Clinical Pharmacology & Biopharmaceutics最新文献

{"title":"Absorption process of salazosulfapyridine in human intestinal epithelial cells and rat intestine","authors":"K. Naruhashi, Akiko Kamino, E. Ochi, Erina Kusabiraki, M. Ueda, S. Sugiura, Hirokazu Nakanishi, N. Shibata","doi":"10.4172/2167-065X.1000165","DOIUrl":"https://doi.org/10.4172/2167-065X.1000165","url":null,"abstract":"Introduction: Salazosulfapyridine (SASP) is an oral medication used to treat rheumatoid arthritis and inflammatory bowel disease, particularly ulcerative colitis. It has been reported that various transporters such as P-glycoprotein (Pgp) and multidrug resistance-associated protein 2 (MRP2), are involved in the transport of SASP. P-gp and MRP2 are expressed in the brain, intestine, and various tissues in both humans and rats. In the intestine, P-gp limits the absorption of certain drugs, however, its mode of absorptive action with regard to SASP has not, as of yet been studied. The aim of this study was to investigate the intestinal transport of SASP and examine whether transporters such as P-gp and MRP2 are involved in this process. Method: Bidirectional permeability and inhibition transport studies were performed using Caco-2 and T84 cell lines. Transcellular transport studies were conducted using isolated rat intestinal tissue mounted in an Ussing-type chamber. The intestinal absorption was examined using an in-situ closed-loop experiment in rats. Results: SASP showed secretory-directed transport across Caco-2 and T84 cells, as well as rat intestinal tissue. Cyclosporine A (CsA), a P-gp inhibitor, was found to decrease this secretory-directed transport. In the intestinal closedloop experiment, addition of CsA resulted in increased accumulation of SASP; however, this was too miniscule to be considered. The inhibition study showed that both secretory and absorptive transporters sensitive to probenecid are involved in the process of SASP absorption in the small intestine. Conclusion: In the process of SASP absorption in the intestine, CsA-sensitive secretory transporters including P-gp as well as probenecid-sensitive absorptive and secretory-transporters are involved and the total of the absorption of SASP is regulated by these transporters. It is likely that these transporters are coordinated in a complex manner to effectively regulate absorption of SASP and other biochemically similar drugs.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81306503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplex LCMS Bioanalysis of Brentuximab Vedotin, Rituximab and Cetuximab towards Therapeutic Drug Monitoring Application by Combined Calibration Curve Using Fab-Selective Limited Proteolysis nSMOL","authors":"N. Iwamoto, M. Takanashi, A. Hamada, T. Shimada","doi":"10.4172/2167-065X.1000164","DOIUrl":"https://doi.org/10.4172/2167-065X.1000164","url":null,"abstract":"Background: Recently, monoclonal antibody (mAb) bioanalysis using mass spectrometry has begun to be recognized as useful technology for mAbs measurement other than ELISA. We have recently exploited a high-precision method for bioanalysis of monoclonal antibody (mAb) using mass spectrometry. The method is nano-surface and molecular-orientation limited (nSMOL) proteolysis, which is useful for LCMS bioanalysis of many kinds of antibody drugs. Methods: nSMOL is Fab-selective limited proteolysis which consists of the difference of protease nanoparticle diameter (200 nm) and antibody resin pore diameter (100 nm). For limited proteolysis of antibody, Protein A resin (pore: 100 nm) slurry was added to plasma including monoclonal antibody, and the antibody Fc region was immobilized to the resin at 25°C for 10 min with gentle vortexing. Antibody-immobilized resin was washed with PBS, and limited proteolysis was performed with trypsin-conjugated FG beads (diameter: 200 nm). Limited proteolysis of Fab region on antibody was achieved by these two diameter difference. After nSMOL proteolysis, the generated peptides were collected by only simple filtration. Results: In this study, we have demonstrated that the first full validation dataset for bioanalysis using nSMOL of antibody-drug conjugate (ADC), Brentuximab vedotin, in human plasma using nSMOL proteolysis. Full validation using nSMOL proteolysis fulfilled criteria of guideline on bioanalytical method validation in pharmaceutical development for small molecule drug compounds. Conclusions: These results indicate that nSMOL is also significant method for precise quantification of ADC in plasma, such as Brentuximab vedotin. Furthermore, we report that nSMOL proteolysis is able to apply for not only single-analyte but also multi-analyte bioanalysis of each mAbs in plasma, so that, nSMOL proteolysis is feasible multiplex bioanalysis for many clinical pharmacokinetic study and therapeutic drug monitoring.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88856282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribavirin Transporter [Ent1] Polymorphism is a Pretreatment Predictorof Virologic Response: The Specific Role of Donor Liver Transporter","authors":"V. Giannelli, M. Simmaco, L. Lionetto, G. Gentile, M. Giusto, F. Ponziani, A. Gasbarrini, U. Visco-Comandini, A. Pellicelli, S. Corradini, A. Molinaro, E. Biliotti, M. Merli, G. Taliani","doi":"10.4172/2167-065X.1000163","DOIUrl":"https://doi.org/10.4172/2167-065X.1000163","url":null,"abstract":"The genetic polymorphism of Equilibrative Nucleoside Transporter 1 [ENT1] is involved in ribavirin cellular uptake and it could positively enhance antiviral treatment response. The liver transplant setting offers the unique opportunity to selectively observe the effect(s) of the donor liver ENT1 gene on HCV treatment outcome. We aimed at studying donor polymorphism of ENT1 and HCV therapy outcome in transplanted patients. The role of ribavirin plasma concentration was evaluated. 39 patients after HCV recurrence were included. Genotyping of donor ENT1 and of IL-28B was performed in donor liver samples by RNA PCR. Allelic frequencies of liver ENT1 were: AA 43.6%; AG 28.2%; GG 28.2%. GG genotype was associated with rapid [RR=8; 95% CI 1.6-38; p=0.01] and sustained virological response [RR=9.5; 95% CI 1.6-53; p=0.01]. In multivariate analysis, GG genotype and a ribavirin plasma concentration >2.0 ng/mL at week 12 were independently associated with sustained virological response. In conclusion, the genetic polymorphism of ENT influences treatment response and a pre-treatment determination of its activity could help to predict treatment response in HCV patients.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76531876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychotropic Medications Metabolized by Cytochromes P450 (CYP) 2D6 Enzyme and Relevant Drug Interactions","authors":"G. Ayano","doi":"10.4172/2167-065X.1000162","DOIUrl":"https://doi.org/10.4172/2167-065X.1000162","url":null,"abstract":"Psychotropic medications metabolized by cytochromes P450 (CYP) 2D6 are reviewed, and the possible relevance of this metabolism to drug-drug interactions is discussed. CYP2D6 is a member of the cytochrome P450 super family and it plays a primary role in the metabolism of more than 70 substrate medications, belonging to classes such as antidepressants, antipsychotics, mood stabilizers, antiarthemics, beta blockers antiemetics, opoid and Sedative/ hypnotics. It is responsible for the metabolism of about 25% of the commonly prescribed drugs. CYP2D6 Primarily metabolizes four of the typical antipsychotic medications, such as haloperidol, chlorpromazine, thioridazine and perphenazine, and risperidone from second generation antipsychotics. Nortriptyline, paroxetine, fluoxetine, venlafaxine and desipramine are antidepressants which are primarily metabolized by CYP2D6. Propranolol, metoprolol, timolol and alperolol are among the common beta blockers which are primarily metabolized by CYP2D6. Drugs which are metabolized by CYP2D6 may inhibit or induce the action of the enzyme. Drugs that inhibit CYP2D6 will predictably increase the plasma concentrations of the medications or decrease in clearance of substrates. Drugs such as bupropion, Fluoxetine, Paroxetine, norethindrone Citalopram, Escitalopram, Sertraline, Fluvoxamine, Nefazodone, Venlafaxine, clomipramine, cocaine, quinidine, and ranitidine are inhibiters of CYP2D6 enzyme. Unlike CYP1A2, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 enzymes which together with CYP2D6 metabolizes 90 percent of drugs CYP2D6 has no significant inducers.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87549463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II Study Evaluating the Effect of Concomitant Ramucirumab on the Pharmacokinetics of Docetaxel in Patients with Advanced Solid Tumors","authors":"M. Stein, L. Chow, David C. Smith, D. Shepard, D. Wan, J. Powderly, A. Chaudhary, Yong Lin, L. Gao","doi":"10.4172/2167-065X.1000161","DOIUrl":"https://doi.org/10.4172/2167-065X.1000161","url":null,"abstract":"Background: Ramucirumab is a human IgG1 monoclonal antibody that specifically targets the vascular endothelial growth factor receptor-2. The primary objective of this study was to investigate the effect of concomitant ramucirumab on the pharmacokinetics of docetaxel. Methods: Patients with metastatic or locally advanced malignant solid tumors resistant to standard therapy or for which no standard therapy was available were recruited. Patients received docetaxel 75 mg/m2 and ramucirumab 10 mg/kg on day 1 of a 3-week cycle. In cycle 1, docetaxel was administered alone; in cycle 2 and subsequent cycles, ramucirumab was administered followed by docetaxel. Blood was drawn immediately before and at regular intervals after infusions for cycles 1 and 2 to determine docetaxel and ramucirumab concentrations. Results: Docetaxel pharmacokinetic parameters were assessed in 18 patients. The dose-normalized area under the plasma concentration versus time curve from time zero extrapolated to infinity and maximum plasma drug concentration of docetaxel during cycle 2 were similar to those when docetaxel was administered alone during cycle 1, with geometric least squares means ratios of 0.97 (90% CI: 0.84, 1.10) for the area under the plasma concentration versus time curve from time zero extrapolated to infinity and 1.14 (90% CI: 0.84, 1.55) for the maximum plasma drug concentration. Of the 22 patients who received any dose of study drug, the most commonly reported treatment-emergent adverse events included nausea (12 patients, 54.5%), fatigue, leukopenia, and neutropenia (each in nine patients, 40.9%). The most commonly reported grade ≥ 3 treatment-emergent adverse events were leukopenia and neutropenia (each in seven patients, 31.8%). Conclusions: Coadministration of ramucirumab had no effect on the pharmacokinetics of docetaxel. The incidence and severity of treatment-emergent adverse events were consistent with the known safety profiles of docetaxel and ramucirumab.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89340092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artemisinin protected neuronal cells from oxidative insult via the MAPK pathway","authors":"Wenhua Zheng Fang Jiankang Wan Pei Xu Jinying CheongMeng Chong, Philip Lazarovici","doi":"10.4172/2167-065X.C1.019","DOIUrl":"https://doi.org/10.4172/2167-065X.C1.019","url":null,"abstract":"","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74845850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical development of PfSPZ vaccine: A highly protective, well-tolerated and safe vaccine for the prevention of malaria in travelers and for the elimination of malaria from endemic areas","authors":"T. Richie","doi":"10.4172/2167-065X.C1.018","DOIUrl":"https://doi.org/10.4172/2167-065X.C1.018","url":null,"abstract":"","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76749863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of an Oral Supplementation Based on Orthosilicic Acid Choline-Stabilized on Skin, Hair and Nails: A Clinical Study with Objective Approach","authors":"P. M. Campos, G. Favaretto","doi":"10.4172/2167-065X.1000160","DOIUrl":"https://doi.org/10.4172/2167-065X.1000160","url":null,"abstract":"In recent years, various dietary supplements have been released in the market with the promise of health benefits and functional properties. New trends involving nutrition have been highlighted due to the potential effects of certain food ingredients in the cutaneous aging process, the healthy appearance of skin, hair and nails. Looking at the growing demand for improvement in the appearance of hair, skin and nails and the increased interest of the population by use of nutricosmetics, the aim of this study was to evaluate an oral supplementation with orthossilicic acid choline-stabilized. For this, it was done a randomized, placebo-controlled clinical test. After approval of the ethics committee, were selected 60 women, aged 40 and 65 and they were divided into two groups (treatment and placebo). The daily dose of the supplement for evaluation was 400 mg of orthossilicic acid choline-stabilized for a period of 3 months. Analyzes were done before the treatment (basal-T0) and after 30, 60 and 90 days of treatment and it were evaluated the structural characteristics of the dermis, the mechanical properties of hair and the perception of effectiveness by the volunteers. According to the results, it was observed for the treatment group an increase in echogenicity of the dermis after 90 days of treatment. Thus, it proved that the treatment increased the density of the skin. In addition, the high resolution images showed improvement in skin micro relief and an improvement in skin roughness. There was also increased resistance of the hair and volunteers of treatment group reported improvement in skin, hair and nails. Finally, the oral supplementation of the nutricosmetic with orthossilicic acid choline-stabilized can be suggested as an effective product to increase skin density and to improve hair and nails conditions, complementary to topical treatments.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75860751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editor note on Pharmacokinetics and Dynamics of Novel Drugs","authors":"A. Al-Achi","doi":"10.4172/2167-065X.1000E125","DOIUrl":"https://doi.org/10.4172/2167-065X.1000E125","url":null,"abstract":"","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90940906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Recombinant Soluble Human Thrombomodulin in Subjects with Normal and Various Impaired Renal Function","authors":"Shinichiro Shirae, Y. Osawa, T. Marbury, K. Tsuruta","doi":"10.4172/2167-065X.1000159","DOIUrl":"https://doi.org/10.4172/2167-065X.1000159","url":null,"abstract":"Background: Non-clinical and clinical studies showed efficacy of thrombomodulin alfa for disseminated intravascular coagulation, and its potential efficacy for severe sepsis and coagulopathy. Thrombomodulin alfa is excreted primarily via the kidney and renal function is known to affect the clearance. However the dosing adjustments for patients with renal dysfunction were not warranted, except for patients on hemodialysis, who had not been studied well. This study was conducted to assess the effect of renal impairment on the exposure of thrombomodulin alfa and to support a dosing rationale in patients with renal impairment especially patients on hemodialysis. Material and methods: Forty subjects with varying renal function participated in 5 groups. Each subject received one intravenous bolus injection of 0.06 mg/kg thrombomodulin alfa. The PK parameters were analyzed by a twocompartment model. The plasma concentration following multiple doses was simulated based on the PK parameters in each subject and various renal function groups. The predicted maximum plasma concentration (Cmax) was compared with the maximum non-toxic concentration (5,400 ng/mL). Results: Following multiple dose simulations of six, once-daily intravenous bolus injections of 0.06 mg/kg thrombomodulin alfa, the predicted mean Cmax in subjects with normal renal function, and mild, moderate, or severe renal impairment and on hemodialysis was 2,030, 2,350, 2,410, 3,710, 3,180 ng/mL, respectively. The highest individual simulated Cmax was 4,730 ng/mL, hence no renal function groups or no individually simulated Cmax exceeded the maximum non-toxic concentration. Conclusion: Although renal impairment was associated with increased exposure of thrombomodulin alfa, no dose adjustment is required for patients with renal impairment including patients on hemodialysis.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76084576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}