1,351 results match your criteria pharmacokinetics irinotecan

Contribution of the Gut Microbiome to Drug Disposition, Pharmacokinetic and Pharmacodynamic Variability.

Clin Pharmacokinet 2021 May 7. Epub 2021 May 7.

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, MC 0657, La Jolla, San Diego, CA, 90293-0657, USA.

The trillions of microbes that make up the gut microbiome are an important contributor to health and disease. With respect to xenobiotics, particularly orally administered compounds, the gut microbiome interacts directly with drugs to break them down into metabolic products. In addition, microbial products such as bile acids interact with nuclear receptors on host drug-metabolizing enzyme machinery, thus indirectly influencing drug disposition and pharmacokinetics. Read More

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Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen.

Cancer Chemother Pharmacol 2021 Apr 28. Epub 2021 Apr 28.

SMARTc, Centre de Recherche en Cancérologie de Marseille (CRCM), Faculté de Pharmacie, INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Marseille, France.

Purpose: The aim of the present study was to characterize the pharmacokinetics of irinotecan and its four main metabolites (SN-38, SN-38G, APC and NPC) in metastatic colorectal cancer patients treated with FOLFIRI and FOLFIRINOX regimens and to quantify and explain the inter-individual pharmacokinetic variability in this context.

Methods: A multicenter study including 109 metastatic colorectal cancer patients treated with FOLFIRI or FOLFIRINOX regimen, associated or not with a monoclonal antibody, was conducted. Concentrations of irinotecan and its four main metabolites were measured in 506 blood samples during the first cycle of treatment. Read More

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The Use of Subgroup Disproportionality Analyses to Explore the Sensitivity of a Global Database of Individual Case Safety Reports to Known Pharmacogenomic Risk Variants Common in Japan.

Drug Saf 2021 Apr 10. Epub 2021 Apr 10.

Uppsala Monitoring Centre, Box 1051, 75140, Uppsala, Sweden.

Introduction: Genetic variations of enzymes that affect the pharmacokinetics and hence effects of medications differ between ethnicities, resulting in variation in the risk of adverse drug reactions (ADR) between different populations. Previous work has demonstrated that risk-group considerations can be incorporated into approaches of statistical signal detection. It is unknown whether databases of individual case safety reports (ICSRs) are sensitive to pharmacogenomic differences between populations. Read More

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Self-Monitoring and Self-Delivery of Self-Assembled Fluorescent Nanoparticles in Cancer Therapy.

Int J Nanomedicine 2021 29;16:2487-2499. Epub 2021 Mar 29.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People's Republic of China.

Purpose: Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer. Read More

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Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology.

Pharmaceutics 2021 Mar 30;13(4). Epub 2021 Mar 30.

Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France.

Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K/AkT/mTor pathway has stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with other antineoplastic agents. However, in cancer, there is no consensus on sirolimus TDM. Read More

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Possible roles of intestinal P-glycoprotein and cytochrome P450 3A on the limited oral absorption of irinotecan.

J Pharm Pharmacol 2021 Mar;73(2):178-184

Department of Pharmacy, University of Miyazaki Hospital, Miyazaki, Japan.

Objectives: Irinotecan is a widely intravenously used drug for the treatment of certain types of solid tumours. The oral administration of irinotecan has recently been recognized as being a more effective method for the treatment than intravenous administration. However, the limited oral bioavailability of irinotecan poses a problem for its oral delivery. Read More

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Hypertriglyceridemia Induced by Fluorouracil: A Novel Case Report.

Case Rep Oncol 2021 Jan-Apr;14(1):207-211. Epub 2021 Mar 1.

Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan.

We had previously reported on S-1-induced hypertriglyceridemia. Here, we report fluorouracil-induced hypertriglyceridemia in a patient with capecitabine-induced hypertriglyceridemia and the corresponding therapeutic process. A woman in her forties who had experienced grade 3 hypertriglyceridemia due to oxaliplatin + capecitabine was administered fluorouracil ± oxaliplatin + levofolinate calcium + panitumumab; however, grade 4 hypertriglyceridemia occurred after the thirteenth administration. Read More

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Pharmacogenomics and functional imaging to predict irinotecan pharmacokinetics and pharmacodynamics: the predict IR study.

Cancer Chemother Pharmacol 2021 Mar 23. Epub 2021 Mar 23.

Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Australia.

Purpose: Irinotecan (IR) displays significant PK/PD variability. This study evaluated functional hepatic imaging (HNI) and extensive pharmacogenomics (PGs) to explore associations with IR PK and PD (toxicity and response).

Methods: Eligible patients (pts) suitable for Irinotecan-based therapy. Read More

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Repurposing of camptothecin: An esterase-activatable prodrug delivered by a self-emulsifying formulation that improves efficacy in colorectal cancer.

Int J Pharm 2021 Apr 26;599:120399. Epub 2021 Feb 26.

The First Affiliated Hospital, Zhejiang University School of Medicine, NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, Hangzhou, PR China. Electronic address:

The global burden of colorectal cancer (CRC), the third most commonly diagnosed malignancy, continues to rise. Therefore, more effective and less toxic therapies are needed for CRC. CPT-11 (also called irinotecan), the standard-of-care treatment for CRC, has only had limited effects on survival outcomes. Read More

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Effect of UGT1A1, CYP3A and CES Activities on the Pharmacokinetics of Irinotecan and its Metabolites in Patients with UGT1A1 Gene Polymorphisms.

Eur J Drug Metab Pharmacokinet 2021 Mar 23;46(2):317-324. Epub 2021 Feb 23.

Department of Clinical Pharmacy and Experimental Therapeutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

Background And Objectives: Irinotecan (CPT-11) is metabolized to an active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) by carboxylesterase (CES). SN-38 is then converted to the inactive metabolite SN-38 glucuronide (SN-38G) by glucuronosyltransferase 1A1 (UGT1A1). Genetic polymorphisms in UGT1A1 have been associated with altered SN-38 pharmacokinetics, which increase the risk of toxicity in patients. Read More

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A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver.

Drug Deliv 2021 Dec;28(1):240-251

Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Colorectal cancer is one of the most common cancers in the United States and treatment options are limited for patients who develop liver metastases. Several chemotherapeutic regimens have been used for transvascular liver-directed therapy in the treatment of colorectal liver metastases without clear evidence of superiority of one therapy over another. We describe the development of a novel nanoemulsion through combining irinotecan (IRI), a first line systemic agent used for the treatment of colon cancer, with lipiodol, an oily contrast medium derived from poppy seed oil, and evaluated its pharmacokinetic and biodistribution profile as a function of portal venous chemoembolization (PVCE) versus transarterial chemoembolization (TACE) delivery. Read More

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December 2021

Irinotecan and berberine co-delivery liposomes showed improved efficacy and reduced intestinal toxicity compared with Onivyde for pancreatic cancer.

Drug Deliv Transl Res 2021 Jan 15. Epub 2021 Jan 15.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, P. R. China.

Onivyde is the first irinotecan (IRI) nanoliposome that could improve pharmacokinetics and tumor biodistribution of irinotecan. Although FDA approves Onivyde for the treatment of pancreatic cancer patients who are not effective for GEM, the gastrointestinal toxicity caused by Onivyde is still a problem to be solved in clinical application. Berberine (BER), an isoquinolone alkaloid extracted from several different plants, has been reported to exhibit beneficial effect in alleviating intestinal mucositis and generating synergistic anticancer effect in combination with cytotoxic drugs. Read More

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January 2021

Polydopamine Nanoparticles Camouflaged by Stem Cell Membranes for Synergistic Chemo-Photothermal Therapy of Malignant Bone Tumors.

Int J Nanomedicine 2020 14;15:10183-10197. Epub 2020 Dec 14.

Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China.

Purpose: Nanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors. Read More

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January 2021

Albumin-binding prodrugs via reversible iminoboronate forming nanoparticles for cancer drug delivery.

J Control Release 2021 Feb 24;330:362-371. Epub 2020 Dec 24.

Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Zheda Road 38, Hangzhou 310007, China; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, Zhejiang 311215, China. Electronic address:

Albumin-based nanomedicines are important nanoplatforms for cancer drug delivery. The drugs are either physically encapsulated or covalently conjugated to albumin or albumin-based nanosystems. Physical encapsulation is advantageous due to requiring no chemical modification of drug molecules, but many drugs, for instance, camptothecin (CPT) and curcumin (CCM), though very hydrophobic, can't be loaded in or form nanoformulations with albumin. Read More

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February 2021

Pharmacovigilance of herb-drug interactions: A pharmacokinetic study on the combination administration of herbal Kang'ai injection and chemotherapy irinotecan hydrochloride injection by LC-MS/MS.

J Pharm Biomed Anal 2021 Feb 20;194:113784. Epub 2020 Nov 20.

Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, 210009, China; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Chinese herbal drugs are often combined with chemotherapy drugs for the treatment of cancers. However, the combination administrations often do not have scientifically sound bases established on full preclinical and clinical investigations. A commonly used anti-colon-cancer herb-drug pair, irinotecan (CPT-11) hydrochloride injection and Kang'ai (KA) injection was taken as an example to investigate the possible pharmacokinetic interactions between Chinese herbal drugs and chemotherapy injections to determine the potential adverse drug reactions (ADRs). Read More

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February 2021

Effects of Protein and Calorie Restriction on the Metabolism and Toxicity Profile of Irinotecan in Cancer Patients.

Clin Pharmacol Ther 2021 May 6;109(5):1304-1313. Epub 2020 Dec 6.

Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Preclinical data suggests that protein and calorie restriction (PCR) might improve treatment tolerability without impairing antitumor efficacy. Therefore, we have studied the influence of PCR on irinotecan pharmacokinetics and toxicity. In this crossover trial, patients with liver metastases of solid tumors were included and randomized to treatment with irinotecan preceded by 5 days of PCR (~ 30% caloric and ~ 70% protein restriction) during the first cycle and a second cycle preceded by a normal diet or vice versa. Read More

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SFCE-RAPIRI Phase I Study of Rapamycin Plus Irinotecan: A New Way to Target Intra-Tumor Hypoxia in Pediatric Refractory Cancers.

Cancers (Basel) 2020 Oct 20;12(10). Epub 2020 Oct 20.

Pediatric Onco-Hematology Unit, University Hospital of Strasbourg, 67098 Strasbourg, France.

Hypoxic environment is a prognostic factor linked in pediatric cancers to a worse outcome, favoring tumor progression and resistance to treatments. The activation of mechanistic Target Of Rapamycin (mTor)/hypoxia inducible factor (HIF)-1 pathway can be targeted by rapamycin and irinotecan, respectively. Therefore, we designed a phase I trial associating both drugs in pediatric refractory/relapsing solid tumors. Read More

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October 2020

The transport pathway in the ABCG2 protein and its regulation revealed by molecular dynamics simulations.

Cell Mol Life Sci 2021 Mar 26;78(5):2329-2339. Epub 2020 Sep 26.

Department of Biophysics and Radiation Biology, Semmelweis University, Tuzolto u. 37-47, 1094, Budapest, Hungary.

Atomic-level structural insight on the human ABCG2 membrane protein, a pharmacologically important transporter, has been recently revealed by several key papers. In spite of the wealth of structural data, the pathway of transmembrane movement for the large variety of structurally different ABCG2 substrates and the physiological lipid regulation of the transporter has not been elucidated. The complex molecular dynamics simulations presented here may provide a breakthrough in understanding the steps of the substrate transport process and its regulation by cholesterol. Read More

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Hypertriglyceridemia induced by S-1: A novel case report and review of the literature.

J Oncol Pharm Pract 2020 Sep 16:1078155220956691. Epub 2020 Sep 16.

Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan.

Introduction: S-1, a compounding agent of tegafur, gimeracil, and oteracil potassium, is one of the most effective chemotherapeutic agents for colorectal cancer. In this case, following S-1 administration, we observed predominant elevation of serum triglyceride.

Case Report: A 49-year-old man with stage IV transverse colon adenocarcinoma received S-1 + irinotecan + bevacizumab. Read More

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September 2020

Structural Optimization and Enhanced Prodrug-Mediated Delivery Overcomes Camptothecin Resistance in High-Risk Solid Tumors.

Cancer Res 2020 10 24;80(19):4258-4265. Epub 2020 Aug 24.

Division of Oncology, Children's Hospital of Philadelphia, and the University of Pennsylvania/Perelman School of Medicine, Philadelphia, Pennsylvania.

Camptothecins are potent topoisomerase I inhibitors used to treat high-risk pediatric solid tumors, but they often show poor efficacy due to intrinsic or acquired chemoresistance. Here, we developed a multivalent, polymer-based prodrug of a structurally optimized camptothecin (SN22) designed to overcome key chemoresistance mechanisms. The ability of SN22 vs. Read More

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October 2020

A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies.

Eur J Cancer 2020 09 11;137:204-213. Epub 2020 Aug 11.

Departments of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Departments of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; The Departments of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38103, USA.

Background: Talazoparib combined with irinotecan and temozolomide demonstrated efficacy in a murine Ewing sarcoma model. Based on these data, we conducted a phase I trial of talazoparib and irinotecan with/without temozolomide in paediatric patients with recurrent/refractory solid malignancies.

Patients And Methods: Cohorts of 3-6 patients with recurrent/refractory solid malignancies received escalating doses of oral talazoparib and intravenous irinotecan (arm A) and oral talazoparib, oral temozolomide and intravenous irinotecan (arm B) in a 3 + 3 design. Read More

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September 2020

Effect of drug metabolizing enzymes and transporters in Thai colorectal cancer patients treated with irinotecan-based chemotherapy.

Sci Rep 2020 08 10;10(1):13486. Epub 2020 Aug 10.

Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.

Genetic polymorphisms in drug metabolizing enzymes and drug transporters may affect irinotecan toxicity. Although genetic polymorphisms have been shown to influence the irinotecan toxicity, data are limited in Thai population. Thus, the aim of this study was to assess the allele and genotype frequencies and the relationship between CYP3A4/5, DPYD, UGT1A1, ABCB1, and ABCC2 genetic variations and irinotecan-induced toxicity in Thai colorectal cancer patients. Read More

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Synthesis and Characterization of Dendrimer-Based Polysarcosine Star Polymers: Well-Defined, Versatile Platforms Designed for Drug-Delivery Applications.

Biomacromolecules 2020 08 28;21(8):3332-3341. Epub 2020 Jul 28.

Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield SK10 2NA, U.K.

This paper describes the synthesis of star polymers designed for future drug-delivery applications. A generation-5 lysine dendrimer was used as a macroinitiator for the ring-opening polymerization of the sarcosine -carboxyanhydride monomer to produce 32-arm star polymers with narrow molar mass distributions and desirable hydrodynamic size control. Fluorescent dye-labeled polymers were dosed in mice to measure plasma pharmacokinetics. Read More

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Irinotecan-Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview.

Int J Mol Sci 2020 Jul 12;21(14). Epub 2020 Jul 12.

Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland.

Irinotecan has been used in the treatment of various malignancies for many years. Still, the knowledge regarding this drug is expanding. The pharmacogenetics of the drug is the crucial component of response to irinotecan. Read More

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Handling and performance characteristics of a new small caliber radiopaque embolic microsphere.

J Biomed Mater Res B Appl Biomater 2020 10 23;108(7):2878-2888. Epub 2020 Jun 23.

Biocompatibles UK Ltd., a BTG International Group Company, Camberley, Surrey, UK.

The in vitro and in vivo handling and performance characteristics of a small caliber radiopaque embolic microsphere, 40-90 μm DC Bead LUMI™ (LUMI40-90), were studied. Microsphere drug loading and elution and effects on size, suspension, and microcatheter delivery were evaluated using established in vitro methodologies. In vivo evaluations of vascular penetration (rabbit renal artery embolization), long-term biocompatibility and X-ray imaging properties, pharmacokinetics and local tissue effects of both doxorubicin (Dox) and irinotecan (Iri) loaded microspheres (swine hepatic artery embolization) were conducted. Read More

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October 2020

Phase I Study of Ramucirumab Plus Merestinib in Previously Treated Metastatic Colorectal Cancer: Safety, Preliminary Efficacy, and Pharmacokinetic Findings.

Oncologist 2020 11 17;25(11):e1628-e1639. Epub 2020 Jul 17.

University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Lessons Learned: The combination of the antivascular endothelial growth factor receptor 2 monoclonal antibody, ramucirumab, and the type II MET kinase inhibitor, merestinib, is tolerable. Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with metastatic colorectal cancer (mCRC). Further development of this combination would likely necessitate the identification of subsets of patients with mCRC where the clinical benefit is of clinical relevance. Read More

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November 2020

First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients.

Ther Adv Med Oncol 2020 2;12:1758835920926796. Epub 2020 Jun 2.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.

Background: YYB101, a humanized monoclonal antibody against hepatocyte growth factor (HGF), has shown safety and efficacy and . This is a first-in-human trial of this antibody.

Materials And Methods: YYB101 was administered intravenously to refractory cancer patients once every 4 weeks for 1 month, and then once every 2 weeks until disease progression or intolerable toxicity, at doses of 0. Read More

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Tuning the pharmacokinetics and efficacy of irinotecan (IRI) loaded gelatin nanoparticles through folate conjugation.

Int J Pharm 2020 Aug 10;586:119522. Epub 2020 Jun 10.

Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400 094, India. Electronic address:

Gelatin based nanocarriers have major limitation of shorter circulation half-life (t). Present study addressed this issue by conjugating gelatin with folate followed by nanoprecipitation in presence of polysorbate 80 to form folate attached gelatin nanoparticles (GNP-F). The folic acid was conjugated with gelatin through the formation of amide linkage with a maximum conjugation yield of ~69%. Read More

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Characterization of -Iodobenzylguanidine (mIBG) Transport by Polyspecific Organic Cation Transporters: Implication for mIBG Therapy.

Mol Pharmacol 2020 08 2;98(2):109-119. Epub 2020 Jun 2.

Department of Pharmaceutics, University of Washington, Seattle, Washington

Radiolabeled -iodobenzylguanidine (mIBG) is an important radiopharmaceutical used in the diagnosis and treatment of neuroendocrine cancers. mIBG is known to enter tumor cells through the norepinephrine transporter. Whole-body scintigraphy has shown rapid mIBG elimination through the kidney and high accumulation in several normal tissues, but the underlying molecular mechanisms are unclear. Read More

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Oral S-1 with 24-h Infusion of Irinotecan plus Bevacizumab versus FOLFIRI plus Bevacizumab as First-Line Chemotherapy for Metastatic Colorectal Cancer: An Open-Label Randomized Phase II Trial.

Oncology 2020 29;98(9):637-642. Epub 2020 May 29.

Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.

Background: FOLFIRI plus bevacizumab have been widely used as first-line treatment for metastatic colorectal cancer (mCRC). Pharmacokinetics and pharmacodynamics suggested a low dose of irinotecan given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare oral S-1 with a 24-h infusion of irinotecan plus bevacizumab versus FOLFIRI plus bevacizumab. Read More

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September 2020