Publications by authors named "Arne Helland"

34 Publications

Effect of Sleeve Gastrectomy on Buprenorphine Pharmacokinetics: A Planned Case Observation.

Clin Ther 2020 11 25;42(11):2232-2237. Epub 2020 Sep 25.

Department of Clinical Pharmacology, Clinic of Laboratory Medicine, St. Olav University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

Purpose: Bariatric surgery may affect the absorption and metabolism of drugs by various mechanisms. We present a planned case observation of a patient treated with sublingual buprenorphine in an opioid maintenance treatment program, and the observed changes in buprenorphine pharmacokinetics following gastric sleeve surgery.

Methods: Serial blood samples during a dose interval of 24 hours were obtained approximately 1 year preoperatively as well as 1 week, 1 month and 12 months postoperatively and key pharmacokinetic variables were calculated.

Findings: The systemic exposure of buprenorphine (AUC) was relatively stable from the preoperative sampling to 1 week postoperatively (-6.3%), but declined markedly at 1 month (-43%) and 12 months (-42%) postoperatively. The maximum concentration of buprenorphine almost doubled at 1 week postoperatively before returning to baseline values 1 month and 12 months postoperatively.

Implications: This case observation indicates that after sleeve gastrectomy, the systemic exposure of sublingual buprenorphine can decrease. Clinicians should be aware of the possibility of loss of effect and emerging abstinence symptoms following sleeve gastrectomy. We recommend monitoring the patient closely for abstinence symptoms postoperatively and considering measuring serum concentrations of buprenorphine pre- and postoperatively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2020.08.016DOI Listing
November 2020

Establishing Serum Reference Ranges for Antihypertensive Drugs.

Ther Drug Monit 2021 02;43(1):116-125

Department of Pharmacology, Oslo University Hospital.

Background: Therapeutic drug monitoring (TDM) involves the measurement of serum drug concentrations to optimize pharmacotherapy. Traditionally, blood pressure measurements alone, and not TDM, have been used to evaluate the antihypertensive drug response. However, approximately 50% of hypertensive patients treated with lifestyle changes and antihypertensive drugs fail to achieve blood pressure control. Serum drug concentration measurements could be useful to select the optimal drugs in adjusted doses and to identify nonadherence. Implementation of TDM in clinical routine for antihypertensive drugs depends on established serum reference ranges.

Methods: Commonly used antihypertensive drugs were identified based on prescription data. The authors performed a review of authoritative literature on reported serum drug concentrations and calculated expected concentrations from previously reported pharmacokinetic parameters with commonly prescribed daily doses. Finally, serum drug concentrations in samples from patients undergoing antihypertensive treatment were measured.

Results: Serum reference ranges for 24 frequently used antihypertensive drugs were established based on results from 3 approaches.

Conclusions: Serum drug concentration measurements, interpreted in light of the established reference ranges, together with blood pressure measurements and other clinical data, may help identify nonadherent patients and tailor individual antihypertensive treatment when deviant drug responses appear in line with the concept of personalized medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FTD.0000000000000806DOI Listing
February 2021

Stability of 21 Antihypertensive Drugs in Serum Collected in Standard (Nongel) Serum Tubes Versus Tubes Containing a Gel Separator.

Ther Drug Monit 2020 04;42(2):335-340

Department of Clinical Pharmacology, St. Olav University Hospital; and.

Background: Therapeutic drug monitoring of antihypertensive drugs is being increasingly used to optimize treatment and to assess nonadherence. Separator gels are often used in blood collection tubes to facilitate serum or plasma separation from other blood constituents before analyses. Drug adsorption into the separator gel presents a possible pre-analytical cause of falsely low concentrations or false negative results.

Methods: Drug-free blood from blood donors was spiked with therapeutic concentrations of 21 antihypertensive drugs, transferred to serum tubes with and without separator gel (Vacuette gel plastic tubes and plain serum plastic tubes, respectively), and centrifuged. Serum was collected immediately after centrifugation and after 24 and 72 hours of room temperature storage, samples were analyzed in triplicates using liquid chromatography-mass spectrometry.

Results: Serum samples collected immediately after centrifugation or 24 hours later, had the same drug concentrations in the gel and nongel tubes. After 72 hours of room temperature storage, verapamil and lercanidipine serum concentrations were 43% and 29%, respectively, lower in gel tubes than nongel tubes. Canrenone, diltiazem, and bendroflumethiazide showed between 10% and 20% concentration loss in gel tubes, compared with nongel tubes, with the 2 latter observed as unstable also in nongel tubes.

Conclusions: Except for verapamil, lercanidipine, and canrenone, which showed substantial concentration loss in gel tubes, gel tubes may be used for therapeutic drug monitoring purposes for the most commonly used antihypertensive drugs. Transferring serum to gel-free containers immediately after centrifugation minimizes concentration loss; however, bendroflumethiazide and diltiazem are generally unstable at room temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FTD.0000000000000708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077963PMC
April 2020

Drugs of abuse testing – in brief.

Tidsskr Nor Laegeforen 2019 02 25;139(4). Epub 2019 Feb 25.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4045/tidsskr.18.0920DOI Listing
February 2019

Quantification of 21 antihypertensive drugs in serum using UHPLC-MS/MS.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Jul 28;1089:84-93. Epub 2018 Apr 28.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway. Electronic address:

Background: Poor drug adherence in hypertensive patients can lead to treatment failure and increased cardiovascular morbidity, as well as increased costs to society. An analytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MSMS) was developed and validated for use in routine therapeutic drug monitoring (TDM). The method includes 21 antihypertensive drugs or active metabolites from the groups beta blockers (n=5), calcium antagonists (n=5), angiotensin II receptor antagonists (n=4), angiotensin converting enzyme (ACE) inhibitors (n=3) and diuretics (n = 3), in addition to one α1-selective alpha blocker.

Method: A 200 µL serum sample was handled automatically using a pipetting robot. Protein precipitation was performed with 600 µL of 1% formic acid in acetonitrile (v:v) and phospholipid removal was carried out using a Waters OSTRO™ 96-well plate. After evaporation and reconstitution the eluent was injected thrice with different inlet and mass spectrometric methods to cover the different physico-chemical properties of the drugs and the variations in therapeutic concentration ranges between drugs. Acquity UPLC BEH C18 (2.1x50mm, 1.7 µm) column equipped with a corresponding pre-column was used for chromatographic separation. For every analyte an isotopically labelled analogue served as internal standard, except for lisinopril where enalaprilat-d5 was used.

Results: Accuracies were in the range of -13.7 to 13.2% and intra-day and inter-day precisions in the range of 1.1 to 10.5%. The linearity within the calibration ranges expressed as coefficient of determination was higher than 0.995 for all compounds. Matrix effects and recovery efficiencies were within acceptable limits. The limits of quantitation varied from 0.02 to 10.7 µg/L. The stability of the drugs in serum at different conditions was tested. Diltiazem was not stable at 4-8 °C with up to 23.5 % loss after six days. Degradation of atenolol, irbesartan, bendroflumethiazide, hydrochlorothiazide and diltiazem was observed when stored at 30 °C. The suitability of the method was demonstrated in a routine TDM setting, analysing samples from 127 patients undergoing antihypertensive drug treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2018.04.038DOI Listing
July 2018

Systemic Inflammation Complicates the Interpretation of Therapeutic Drug Monitoring of Risperidone.

J Clin Psychopharmacol 2018 06;38(3):263-265

Department of Clinical Pharmacology St Olav University Hospital and Department of Clinical and Molecular Medicine Norwegian University of Science and Technology Trondheim, Norway Department of Psychiatry Møre and Romsdal Hospital Trust Møre and Romsdal, Norway Department of Clinical Pharmacology St Olav University Hospital and Department of Clinical and Molecular Medicine Norwegian University of Science and Technology Trondheim, Norway.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCP.0000000000000873DOI Listing
June 2018

Serum Concentrations of Paliperidone After Administration of the Long-Acting Injectable Formulation.

Ther Drug Monit 2017 12;39(6):659-662

*Department of Clinical Pharmacology, St. Olav University Hospital; and †Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

Background: The pharmacokinetics of long-acting intramuscular paliperidone in a naturalistic setting is not well documented. The objective of this study was to investigate the relationship between dose and serum concentrations of paliperidone using data from a routine therapeutic drug monitoring service.

Methods: Serum concentration measurements in 310 samples from 110 male and 75 female patients receiving depot injections of paliperidone were retrospectively retrieved from the therapeutic drug monitoring database.

Results: The median dose was 100 mg every 28 days. The median concentration/dose (C/D) ratio of paliperidone was 16.1 (nmol/L)/(mg/d), with a 10-90 percentile range of 7.8-31.0 (nmol/L)/(mg/d). Dose-adjusted serum concentrations were 33% higher in patients 65 years or older and more than 50% lower in patients taking the p-glycoprotein inducer carbamazepine. There were no significant effects of sex or dose on the C/D ratio. The median serum concentrations of paliperidone at the end of the dose interval were 31 nmol/L at an intramuscular dose of 50 mg/28 d, 53 nmol/L after a dose of 75 mg/28 d, 59 nmol/L after a dose of 100 mg/28 d, and 93 nmol/L after a dose of 150 mg/28 d. Forty-five percent of the measurements were lower than the suggested therapeutic range of 20-60 ng/mL (47-140 nmol/L).

Conclusions: The data show a 4-fold interindividual difference in dose-adjusted serum concentrations within the 10-90 percentile range and illustrate the significant effects of age and p-glycoprotein induction on the pharmacokinetics of paliperidone. The study also indicates that at least in some patients, it might take longer time than anticipated to reach steady state.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FTD.0000000000000457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690301PMC
December 2017

Two Hospitalizations and One Death After Exposure to Ortho-Fluorofentanyl.

J Anal Toxicol 2017 Oct;41(8):708-709

Department of Clinical Pharmacology, St. Olav University Hospital.

Two young males were hospitalized with miosis and respiratory dysfunction after exposure to a white powder obtained from a foreign source by mail. A few days later, one of the males was found dead at his home. A serum sample from one of the hospitalized patients and a blood sample from the deceased contained ortho-fluorofentanyl in concentrations of 2.5 and 2.4 ng/mL, respectively. It was concluded that death was caused by ortho-fluorofentanyl.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jat/bkx050DOI Listing
October 2017

Enantiomeric separation and quantification of citalopram in serum by ultra-high performance supercritical fluid chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2017 Sep 9;1061-1062:103-109. Epub 2017 Jul 9.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.

A method for enantiomeric separation and quantification of R/S-citalopram in serum was developed and validated using ultra-high performance supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS). Sample preparation prior to UHPSFC-MS/MS analysis consisted of protein precipitation with acidic acetonitrile and filtration through a phospholipid removal plate. The UHPSFC-MS/MS method used an UPC Trefoil CEL2 column with a mobile phase consisting of CO and methanol/acetonitrile (70:30, v/v) with 10mM ammonium acetate. The injection volume was 1μL and run time was 4min. MS/MS detection was performed with positive electrospray ionization and two multiple reaction monitoring transitions (m/z 325.1>262.0 and m/z 325.1>109.0). The calibration range was 5-500nM for each analyte. The between-assay relative standard deviations were in the range of 3.4-4.5%. Recovery was 81-91% and matrix effects ranged from 96 to 101% (corrected with internal standard). After development and initial testing, the method has been successfully implemented in routine use in our laboratory for both separation and quantification of R/S-citalopram in more than 250 serum samples for therapeutic drug monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2017.07.009DOI Listing
September 2017

EtG/EtS in Serum by UHPLC-MS-MS in Suspected Sexual Assault Cases.

J Anal Toxicol 2017 Sep;41(7):618-622

Department of Clinical Pharmacology, St. Olav University Hospital, 7006 Trondheim, Norway.

A method including semi-automated extraction of ethyl glucuronide (EtG) and ethyl sulfate (EtS) from serum followed by ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) has been developed and validated. Sample preparation prior to UHPLC-MS-MS analysis consisted of protein precipitation and filtration through a phospholipid removal plate. Chromatography was achieved using an HSS T3 column and gradient elution with formic acid in water in combination with methanol. The mass spectrometer was monitored in the negative mode with multiple reaction monitoring. Two transitions were monitored for the analytes and one for the deuterated internal standards (ISs). The limits of quantification were 0.025 mg/L for EtG and 0.009 mg/L for EtS. The between-assay relative standard deviations were in the range of 3.8-9.1%, the recovery was 66-102% and matrix effects ranged from 88 to 97% (corrected with IS). Compared to previously published studies, the method presented is semi-automated, uses a simple method for phospholipid removal and has short run times and low limit of quantifications. We analyzed serum samples from 49 female patients presenting to the Sexual Assault Centre at St. Olav University Hospital in Trondheim, Norway, for ethanol, EtG and EtS. EtG and EtS were detected longer than ethanol itself after intake of ethanol, with estimated maximum detection times of >24 h. The ethanol, EtG and EtS concentrations were highly correlated (P < 0.001), but with large inter-individual variations. This study suggests that analysis of EtG and EtS in serum or blood may complement ethanol analysis and shed light on the patient's recent ethanol intake after ethanol itself is no longer detectable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jat/bkx032DOI Listing
September 2017

Studier av alkoholpåvirket kjøring i kjøresimulator.

Authors:
Arne Helland

Tidsskr Nor Laegeforen 2017 Mar 21;137(6):470. Epub 2017 Mar 21.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4045/tidsskr.16.1112DOI Listing
March 2017

[New biomarkers for assesing alcohol consumption].

Tidsskr Nor Laegeforen 2016 Oct 25;136(19):1643-1647. Epub 2016 Oct 25.

Avdeling for klinisk farmakologi St. Olavs hospital og Institutt for laboratoriemedisin, barne- og kvinnesykdommer Norges teknisk-naturvitenskapelige universitet.

Alcohol abuse has significant medical, social and socioeconomic consequences. Alcohol biomarkers may serve as a useful tool in identifying individuals with excessive alcohol consumption in medical as well as medico-legal contexts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4045/tidsskr.16.0056DOI Listing
October 2016

Driving simulator sickness: Impact on driving performance, influence of blood alcohol concentration, and effect of repeated simulator exposures.

Accid Anal Prev 2016 Sep 17;94:180-7. Epub 2016 Jun 17.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.

Simulator sickness is a major obstacle to the use of driving simulators for research, training and driver assessment purposes. The purpose of the present study was to investigate the possible influence of simulator sickness on driving performance measures such as standard deviation of lateral position (SDLP), and the effect of alcohol or repeated simulator exposure on the degree of simulator sickness. Twenty healthy male volunteers underwent three simulated driving trials of 1h's duration with a curvy rural road scenario, and rated their degree of simulator sickness after each trial. Subjects drove sober and with blood alcohol concentrations (BAC) of approx. 0.5g/L and 0.9g/L in a randomized order. Simulator sickness score (SSS) did not influence the primary outcome measure SDLP. Higher SSS significantly predicted lower average speed and frequency of steering wheel reversals. These effects seemed to be mitigated by alcohol. Higher BAC significantly predicted lower SSS, suggesting that alcohol inebriation alleviates simulator sickness. The negative relation between the number of previous exposures to the simulator and SSS was not statistically significant, but is consistent with habituation to the sickness-inducing effects, as shown in other studies. Overall, the results suggest no influence of simulator sickness on SDLP or several other driving performance measures. However, simulator sickness seems to cause test subjects to drive more carefully, with lower average speed and fewer steering wheel reversals, hampering the interpretation of these outcomes as measures of driving impairment and safety. BAC and repeated simulator exposures may act as confounding variables by influencing the degree of simulator sickness in experimental studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aap.2016.05.008DOI Listing
September 2016

Bioavailability of Methadone After Sleeve Gastrectomy: A Planned Case Observation.

Clin Ther 2016 Jun 12;38(6):1532-1536. Epub 2016 May 12.

Department of Clinical Pharmacology, Clinic of Laboratory Medicine, St. Olav University Hospital, Trondheim, Norway; Department of Laboratory Medicine, Children's and Women's Health, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

Objective: Morbidly obese patients on opioid-replacement therapy may be at risk for treatment refusal with regard to bariatric surgery. However, patients on opioid replacement may have the personal skills to facilitate the lifestyle changes required for successful outcomes after bariatric surgery. This planned case observation assessed the effects of sleeve gastrectomy on the pharmacokinetic properties of methadone.

Methods: A white woman in her 40s on methadone maintenance therapy and with morbid obesity was referred for bariatric surgery. Serial blood samples for methadone concentration measurements were obtained before and at 5 days and 1, 7, and 11 months after surgery.

Findings: Serum methadone concentrations increased from before to 5 days after surgery and continued to increase for 7 months thereafter. The predose measurement at 11 months postoperatively suggests a further increase compared with the previous predose measurements.

Implications: Clinicians should beware the potential for altered effects of methadone after bariatric surgery. We recommend that serum concentrations be routinely measured pre- and postoperatively, and that the dose be adjusted according to these measurements and regular clinical assessments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2016.04.033DOI Listing
June 2016

Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, norcodeine, morphine and morphine glucuronides in a series of codeine-related deaths.

Forensic Sci Int 2016 May 4;262:128-37. Epub 2016 Mar 4.

Department of Laboratory Medicine, Children's and Womens's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

This article presents levels and tissue distribution of codeine, codeine-6-glucuronide (C6G), norcodeine, morphine and the morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem blood (peripheral and heart blood), vitreous fluid, muscle, fat and brain tissue in a series of 23 codeine-related fatalities. CYP2D6 genotype is also determined and taken into account. Quantification of codeine, C6G, norcodeine, morphine, M3G and M6G was performed with a validated solid phase extraction LC-MS method. The series comprise 19 deaths (83%) attributed to mixed drug intoxication, 4 deaths (17%) attributed to other causes of death, and no cases of unambiguous monointoxication with codeine. The typical peripheral blood concentration pattern in individual cases was C6G≫codeine≫norcodeine>morphine, and M3G>M6G>morphine. In matrices other than blood, the concentration pattern was similar, although in a less systematic fashion. Measured concentrations were generally lower in matrices other than blood, especially in brain and fat, and in particular for the glucuronides (C6G, M3G and M6G) and, to some extent, morphine. In brain tissue, the presumed active moieties morphine and M6G were both below the LLOQ (0.0080mg/L and 0.058mg/L, respectively) in a majority of cases. In general, there was a large variability in both measured concentrations and calculated blood/tissue concentration ratios. There was also a large variability in calculated ratios of morphine to codeine, C6G to codeine and norcodeine to codeine in all matrices, and CYP2D6 genotype was not a reliable predictor of these ratios. The different blood/tissue concentration ratios showed no systematic relationship with the post-mortem interval. No coherent degradation or formation patterns for codeine, morphine, M3G and M6G were observed upon reanalysis in peripheral blood after storage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.forsciint.2016.02.051DOI Listing
May 2016

Evaluation of measures of impairment in real and simulated driving: Results from a randomized, placebo-controlled study.

Traffic Inj Prev 2016 6;17(3):245-50. Epub 2015 Jul 6.

a Department of Clinical Pharmacology , St. Olav University Hospital , Trondheim , Norway.

Objective: Standard deviation of lateral position (SDLP) is often the primary outcome in experimental studies on impaired driving. However, other measures may be easier and more practical to obtain and reflect a broader range of driving-related behaviors. We wanted to assess the validity and sensitivity of a range of measures in a driving simulator as well as during real driving and compare these to SDLP.

Methods: Twenty healthy male volunteers undertook 6 driving trials each, 3 in a regular car on a closed track resembling rural road conditions and 3 in a simulator with an identical driving scenario. Ethanol was used as impairing substance due to its well-characterized effects on driving. The subjects were tested sober and at blood alcohol concentrations (BAC) of approximately 0.5 and 0.9 g/L. We explored dose-response relationships between BAC and a range of driving-related measures, as well as their BAC-dependent effect sizes.

Results: In simulator driving, ethanol intake increased steering wheel reversal frequency, steering wheel movement measures, average speed, standard deviation of speed, and pedal use frequency. At the test track, only steering wheel movement and standard deviation of speed were significantly correlated to BAC. Likewise, reaction to unexpected incidents and observance of red traffic lights were adversely affected by ethanol in the simulator but not at the test track. Whereas SDLP showed a relatively large effect size that was similar in simulated and real driving, all other measures demonstrated smaller effect sizes, with less pronounced BAC effects on the test track than in the simulator.

Conclusions: The results suggest that the driving-related measures explored in this study are less sensitive to alcohol-mediated driving impairment than SDLP, especially during real (test track) driving. The discrepancy in effect sizes between simulated and real driving may imply low external validity of these measures in simulator studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15389588.2015.1065975DOI Listing
July 2016

Prolonged elimination of paliperidone after administration of paliperidone palmitate depot injections.

J Clin Psychopharmacol 2015 Feb;35(1):95-6

Department of Clinical Pharmacology St Olav University Hospital Trondheim, Norway Division of Mental Health Care St Olav University Hospital Trondheim, Norway Department of Laboratory Medicine Children's and Women's Health Norwegian University of Science and Technology Trondheim, Norway.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCP.0000000000000240DOI Listing
February 2015

Ethanol and drug findings in women consulting a Sexual Assault Center--associations with clinical characteristics and suspicions of drug-facilitated sexual assault.

J Forensic Leg Med 2013 Aug 25;20(6):777-84. Epub 2013 Jun 25.

Department of Public Health and General Practice, Norwegian University of Science and Technology, P.O. Box 8905, N-7491 Trondheim, Norway.

The purpose of the study was to describe toxicological findings among women seeking health care after sexual assault, and to assess the relationship with so-called proactive DFSA (drug facilitated sexual assault). We also explored associations between ethanol in blood/urine and background data, assault characteristics, and clinical findings. We conducted a retrospective, descriptive study of female patients ≥ 12 years of age consulting the Sexual Assault Center at St. Olavs University Hospital, Trondheim, Norway. They were examined between July 1, 2003 and December 31, 2010, and urine and/or blood were analyzed for ethanol and selected medicinal/recreational drugs. Among the 264 patients included, ethanol and/or drugs were detected in 155 (59%). Of the 50 patients (19%) testing positive for drugs other than ethanol, benzodiazepines/benzodiazepine-like drugs were found in 31, central stimulants in 14, cannabinoids in 13 and opioids in nine. None tested positive for gamma-hydroxybutyrate (GHB). In total, 57 patients (22%) suspected proactive DFSA, but only five had findings of sedative drugs that were not accounted for by self-reported voluntary intake. No cases could unequivocally be attributed to proactive DFSA. Among the 120 patients tested for ethanol within 12 h after the assault, 102 were positive. The median estimated blood alcohol concentration (BAC) at the time of assault was 1.87 g/L. Patients testing positive for ethanol more often reported a public place of assault and a stranger assailant. Higher estimated BAC at the time of assault was associated with higher frequency of suspecting proactive DFSA. Ethanol was the most prevalent toxicological finding in urine/blood from victims of sexual assault, and high ethanol concentrations were often detected. Among the patients suspecting proactive DFSA, very few had sedative drug findings not explained by voluntary intake. It seems like opportunistic DFSA, rather than proactive DFSA dominate among the sexually assaulted attending our SAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jflm.2013.05.005DOI Listing
August 2013

EtG/EtS in Urine from sexual assault victims determined by UPLC-MS-MS.

J Anal Toxicol 2013 May 6;37(4):227-32. Epub 2013 Mar 6.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

In cases of sexual assault, victims often present too late for the detection of ethanol in biological samples. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method was developed and validated for the determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine. Sample preparation prior to UPLC-MS-MS analysis was a simple sample dilution. The calibration ranges were 0.2-20 mg/L, and between-assay relative standard deviations were in the range of 0.7-7.0% at concentrations of 0.3, 3.0 and 7.0 mg/L. Urine samples were analyzed from 59 female patients presenting to the Sexual Assault Centre at St. Olav University Hospital in Trondheim, Norway between November 2010 and October 2011. EtG and EtS results were fully concordant, and positive in 45 of the 48 cases with self-reported alcohol intake. In contrast, ethanol was detectable in only 20 of these cases, corresponding to sensitivities of 94 and 42%, respectively. Of the patients reporting no alcohol intake, none had positive EtG/EtS findings. These data show that analysis of EtG and EtS greatly increases the detection window of alcohol ingestion in cases of sexual assault, and may shed additional light on the involvement of ethanol in such cases. The victims' self-reported intake of alcohol seems to be reliable in this study, according to the EtG/EtS findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jat/bkt008DOI Listing
May 2013

Comparison of driving simulator performance with real driving after alcohol intake: a randomised, single blind, placebo-controlled, cross-over trial.

Accid Anal Prev 2013 Apr 28;53:9-16. Epub 2013 Jan 28.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

The purpose of this study was to establish and validate a driving simulator method for assessing drug effects on driving. To achieve this, we used ethanol as a positive control, and examined whether ethanol affects driving performance in the simulator, and whether these effects are consistent with performance during real driving on a test track, also under the influence of ethanol. Twenty healthy male volunteers underwent a total of six driving trials of 1h duration; three in an instrumented vehicle on a closed-circuit test track that closely resembled rural Norwegian road conditions, and three in the simulator with a driving scenario modelled after the test track. Test subjects were either sober or titrated to blood alcohol concentration (BAC) levels of 0.5g/L and 0.9g/L. The study was conducted in a randomised, cross-over, single-blind fashion, using placebo drinks and placebo pills as confounders. The primary outcome measure was standard deviation of lateral position (SDLP; "weaving"). Eighteen test subjects completed all six driving trials, and complete data were acquired from 18 subjects in the simulator and 10 subjects on the test track, respectively. There was a positive dose-response relationship between higher ethanol concentrations and increases in SDLP in both the simulator and on the test track (p<0.001 for both). In the simulator, this dose-response was evident already after 15min of driving. SDLP values were higher and showed a larger inter-individual variability in the simulator than on the test track. Most subjects displayed a similar relationship between BAC and SDLP in the simulator and on the test track; however, a few subjects showed striking dissimilarities, with very high SDLP values in the simulator. This may reflect the lack of perceived danger in the simulator, causing reckless driving in a few test subjects. Overall, the results suggest that SDLP in the driving simulator is a sensitive measure of ethanol impaired driving. The comparison with real driving implies relative external validity of the simulator.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aap.2012.12.042DOI Listing
April 2013

[Potentially addictive drugs on reimbursable prescription for chronic severe pain].

Tidsskr Nor Laegeforen 2013 Jan;133(2):150-4

Institutt for laboratoriemedisin, barne- og kvinnesykdommer, Norges teknisk-naturvitenskapelige universitet, Norway.

Background: Changes in the Norwegian drug reimbursement system in 2008 included the establishment of a new reimbursement code (-71) which authorises coverage of expenditures for potentially addictive drugs in patients with severe, predominantly non-malignant, chronic pain. This reform has hitherto not been evaluated.

Material And Method: We assessed national data on drug reimbursements in accordance with code -71 for the period 2008-2011, and anonymised copies of all confirmation letters granting reimbursements according to code -71 in Central Norway (three counties) for 2010. Approximately 1300 individual applicants' gender and age, diagnosis, potentially addictive drug applied for, drug dose, and identity and specialty of the prescribing physician, were recorded.

Results: From the time of establishment, reimbursement code -71 has been utilised by an increasing number of individuals, encompassing close to 10,000 subjects in 3rd quarter 2011. Almost one-third of the approved applications were for pregabalin, and the rest were for various opioids. The diagnoses were most often derived from the musculoskeletal and nervous systems, and were often nonspecific. A considerable number of treatment regimens were not in accordance with current principles for the management of chronic non-malignant pain, and drug doses were at times remarkably high.

Interpretation: Aspects of this drug reimbursement regulation should be closely monitored, and may be in need of changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4045/tidsskr.12.0658DOI Listing
January 2013

[Quetiapine and the potential for abuse].

Tidsskr Nor Laegeforen 2012 Aug;132(14):1619-20

RELIS Midt-Norge, Avdeling for klinisk farmakologi, St. Olavs hospital, Norway.

Quetiapine is an atypical antipsychotic licensed for the treatment of schizophrenia and bipolar disorder and as an adjunctive for patients with unipolar depression. Case reports suggest a potential for drug abuse, especially among individuals with prior or current abuse of other substances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4045/tidsskr.11.1522DOI Listing
August 2012

Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine-related deaths.

Forensic Sci Int 2012 Jul 28;220(1-3):6-11. Epub 2012 Jan 28.

Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Compared to morphine and morphine-6-glucuronide (M6G), codeine and its other major metabolites codeine-6-glucuronide and norcodeine have weak affinity to opioid μ-receptors. Analgesic effects of codeine are thus largely dependent on metabolic conversion to morphine by the polymorphic cytochrome P450 isoenzyme 2D6 (CYP2D6). How this relates to toxicity and post-mortem whole blood levels is not known. This paper presents a case series of codeine-related deaths where concentrations of morphine, M6G and morphine-3-glucuronide (M3G), as well as CYP2D6 genotype, are taken into account. Post-mortem toxicological specimens from a total of 1444 consecutive forensic autopsy cases in Central Norway were analyzed. Among these, 111 cases with detectable amounts of codeine in femoral blood were identified, of which 34 had femoral blood concentrations exceeding the TIAFT toxicity threshold of 0.3mg/L. Autopsy records of these 34 cases were retrieved and reviewed. In the 34 reviewed cases, there was a large variability in individual morphine to codeine concentration ratios (M/C ratios), and morphine levels could not be predicted from codeine concentrations, even when CYP2D6 genotype was known. 13 cases had codeine concentrations exceeding the TIAFT threshold for possibly lethal serum concentrations (1.6 mg/L). Among these, 8 individuals had morphine concentrations below the toxic threshold according to TIAFT (0.15 mg/L). In one case, morphine as well as M6G and M3G concentrations were below the limit of detection. A comprehensive investigation of codeine-related fatalities should, in addition to a detailed case history, include quantification of morphine and morphine metabolites. CYP2D6 genotyping may be of interest in cases with unexpectedly high or low M/C ratios.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.forsciint.2012.01.019DOI Listing
July 2012

[Baclofen for alcohol addiction].

Tidsskr Nor Laegeforen 2011 Nov;131(21):2132-3

Avdeling for klinisk farmakologi, St. Olavs hospital, Norway.

Baclofen is approved for muscle spasms and cerebral spasticity. Several studies have recently investigated the use of baclofen for alcohol withdrawal symptoms and as an abstinence-promoting agent in alcohol-dependent subjects. The evidence is too weak to recommend baclofen for alcohol withdrawal, and drugs with better documentation such as benzodiazepines and carbamazepine should be preferred for this indication. The evidence for the use of baclofen to prevent relapse to drinking in alcohol dependence is somewhat conflicting, but the drug could be considered as a therapeutic option in case of conservative measures and approved drugs such as disulfiram and acamprosate having insufficient effect. Despite enthusiastic appraisal in case reports, the use of baclofen in high doses to suppress alcohol craving cannot be recommended due to insufficient evidence. Trials that may resolve this issue are underway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4045/tidsskr.11.0584DOI Listing
November 2011

Death of a 10-month-old boy after exposure to ethylmorphine.

J Forensic Sci 2010 Mar 11;55(2):551-3. Epub 2010 Feb 11.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

Ethylmorphine, an opiate that is partially metabolized to morphine, is a common ingredient in antitussive preparations. We present a case where a 10-month-old boy was administered ethylmorphine in the evening and found dead in bed the following morning. Postmortem toxicological analyses of heart blood by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed the presence of ethylmorphine and morphine at concentrations of 0.17 muM (0.054 mg/L) and 0.090 muM (0.026 mg/L), respectively. CYP2D6 genotyping showed that the deceased had an extensive metabolizer genotype, signifying a "normal" capacity for metabolizing ethylmorphine to morphine. The autopsy report concluded that death was caused by a combination of opiate-induced sedation and weakening of respiratory drive, a respiratory infection, and a sleeping position that could have impeded breathing. This is the first case report where the death of an infant has been linked to ethylmorphine ingestion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1556-4029.2009.01294.xDOI Listing
March 2010

[Drug treatment of alcohol withdrawal].

Tidsskr Nor Laegeforen 2008 May;128(10):1182-4

Avdeling for klinisk farmakologi, St. Olavs Hospital, 7006 Trondheim.

View Article and Find Full Text PDF

Download full-text PDF

Source
May 2008