Publications by authors named "Kei Omoda"

4 Publications

  • Page 1 of 1

Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene.

Oncol Lett 2012 Mar 22;3(3):694-698. Epub 2011 Dec 22.

Department of Pharmacy, Osaka Rosai Hospital, Sakai, Osaka 591-8025.

In irinotecan (CPT-11)-based chemotherapy, neutropenia and diarrhea are often induced. In the present study, the clinical significance of the concentration ratios of 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronide (SN-38G) and SN-38 in the plasma in predicting CPT-11-induced neutropenia was examined. A total of 17 patients with colorectal cancer and wild-type UDP-glucuronosyltransferase (UGT)1A1 gene were enrolled and treated with CPT-11 as part of the FOLFIRI regimen [CPT-11 and fluorouracil (5-FU)]. Blood was taken exactly 15 min following a 2-h continuous infusion of CPT-11. Plasma concentrations of SN-38, SN-38G and CPT-11 were determined by a modified high-performance liquid chromatography (HPLC) method. The median, maximum and minimum values of plasma SN-38G/SN-38 ratios were 4.25, 7.09 and 1.03, respectively, indicating that UGT activities are variable among patients with the wild-type UGT1A1 gene. The plasma SN-38G/SN-38 ratios decreased with an increase in the trial numbers of chemotherapy (r=0.741, p=0.000669), suggesting that CPT-11 treatment suppresses UGT activity, and the low plasma SN-38G/SN-38 ratios resulted in the induction of greater neutropenia. However, in this analysis, 2 clearly separated regression lines were observed between plasma SN-38G/SN-38 ratios and neutropenia induction. In conclusion, UGT activity involved in SN-38 metabolism is variable among patients with the wild-type UGT1A1 gene, and each CPT-11 treatment suppresses UGT activity. One-point determination of the plasma SN-38G/SN-38 ratio may provide indications for the prediction of CPT-11-induced neutropenia and adjustment of the optimal dose, although further studies are required.
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http://dx.doi.org/10.3892/ol.2011.533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362497PMC
March 2012

Evaluation of clinical efficacy of Maeda's nomogram for vancomycin dosage adjustment in adult Japanese MRSA pneumonia patients.

Drug Metab Pharmacokinet 2006 Feb;21(1):54-60

Department of Pharmacy, Okayama Rousai General Hospital, Japan.

The clinical efficacy of Maeda's nomogram for vancomycin dosage adjustment was evaluated by comparison with a standard dosage regimen (package insert information: vancomycin dose reduced in elderly patients and patients with renal dysfunction, with Moellering's nomogram used for renal-dysfunction patients) in adult Japanese MRSA pneumonia patients. Using Maeda's nomogram, the vancomycin dose is fixed at 1,000 mg while the dosing interval is varied in accordance with individual creatinine clearance. Using a standard dosage regimen, 5 patients out of 27 (18.5%) achieved target plasma levels of vancomycin (25-40 microg/mL for peak and 5-15 microg/mL for trough) within 2-6 days. Using Maeda's nomogram, 38 patients out of 53 (71.7%) achieved target levels in that time. A higher clinical response (complete resolution of all signs and symptoms of MRSA infection) to vancomycin therapy was also obtained with Maeda's nomogram when evaluated approximately 2-weeks after discontinuation of vancomycin therapy (43.4% versus 18.5% for the standard regimen). In conclusion, the Maeda's nomogram regimen with a 1,000 mg vancomycin dose was shown to achieve target plasma levels of vancomycin at a higher rate and provide higher clinical efficacy in vancomycin therapy of MRSA pneumonia patients, as compared with the currently available standard dosage regimen.
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http://dx.doi.org/10.2133/dmpk.21.54DOI Listing
February 2006

Increased erythrocyte distribution of valproic acid in pharmacokinetic interaction with carbapenem antibiotics in rat and human.

J Pharm Sci 2005 Aug;94(8):1685-93

Department of Pharmaceutics and Therapeutics, Programs for Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

Carbapenem antibiotics cause pharmacokinetic interaction with valproic acid (VPA) in clinical pharmacotherapy. Here, we investigated the mechanism of interaction from the viewpoint of erythrocyte distribution of VPA in rats and humans. Imipenem or panipenem was administered intravenously and then VPA intravenously or into the intestinal lumen in rats. Both imipenem and panipenem significantly decreased plasma VPA levels. In contrast, these antibiotics did not affect, or rather increased, VPA levels in whole blood, and increased the erythrocyte distribution of VPA in vivo. In clinical, two patients receiving VPA were given imipenem intravenously, because of intractable infectious diseases. Imipenem lowered plasma VPA levels by approximately 40%-60% of original levels, and increased the erythrocyte distribution of VPA, as observed in rats. In conclusion, the pharmacokinetic interaction between VPA and carbapenem antibiotics, in which plasma VPA levels were markedly reduced, may partly be derived from the increased erythrocyte distribution of VPA.
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http://dx.doi.org/10.1002/jps.20338DOI Listing
August 2005

Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C.

Ther Drug Monit 2004 Feb;26(1):9-15

Department of Pharmacy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.

The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.
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http://dx.doi.org/10.1097/00007691-200402000-00004DOI Listing
February 2004
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