The influence of fibrate initiation on INR and warfarin dose in patients receiving chronic warfarin therapy
The objective of this study was to evaluate warfarin dose and international normalized ratio (INR) response among a large sample of patients receiving chronic warfarin who initiated a fibrate. This was a retrospective, one-sample, pre-to-post study. Adult patients who were receiving chronic warfarin therapy at the time of gemfibrozil or fenofibrate dispensing between 1/1/2000 and 3/31/2016 were included. Patients had at least one and two therapeutic INRs during the 90 days prior to (baseline) and after (follow-up), respectively, fibrate initiation. Comparison of stable warfarin dose:INR ratio between the baseline and follo...
Source: Journal of Thrombosis and Thrombolysis - April 21, 2018 Category: Hematology Source Type: research
Implications of intercorrelation between hepatic CYP3A4 ‐CYP2C8 enzymes for the evaluation of drug–drug interactions: a case study with repaglinide
ConclusionsThe present study demonstrates via a systematic investigation that population‐based PBPK modelling incorporating intercorrelation led to more consistent estimation of extreme values than those observed in interindividual variabilities of clearance and DDI. As the intercorrelations more realistically reflect enzyme abundances, virtual population studies involving PBPK and DDI should avoid using Monte Carlo assignment of enzyme abundance. (Source: British Journal of Clinical Pharmacology)
Source: British Journal of Clinical Pharmacology - March 6, 2018 Category: Drugs & Pharmacology Authors: Kosuke Doki, Adam S. Darwich, Brahim Achour, Aleksi Tornio, Janne T. Backman, Amin Rostami ‐Hodjegan Tags: DRUG INTERACTIONS Source Type: research
The Emerging Role of Inflammation in Cardiovascular Disease.
CONCLUSIONS: Patients with elevated inflammatory markers such as hsCRP are at risk for ASVCD events. Several drug classes have shown the ability to decrease hsCRP levels, but the extent to which this reduces ASCVD events in lieu of other drug mechanisms was not clear. Canakinumab specifically targets the inflammatory process in ASCVD and was proven to be effective in preventing ASCVD events in patients with elevated hsCRP levels.
PMID: 29557210 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)
Source: The Annals of Pharmacotherapy - March 1, 2018 Category: Drugs & Pharmacology Authors: Martinez BK, White CM Tags: Ann Pharmacother Source Type: research
Investigation of pharmaceutically active compounds in an urban receiving water: Occurrence, fate and environmental risk assessment.
Abstract
Pharmaceutically active compounds (PhACs) recently have been recognized to constitute a health risk for aquatic ecosystems. The major pathways of PhACs to enter the aquatic environment are excretion and discharge of effluents through sewage treatment plants (STPs). The occurrence, bioaccumulation and risk assessment of lipophilic PhACs, including erythromycin, ketoconazole, indomethacin, diclofenac, gemfibrozil, bezafibrate, propranolol, carbamazepine, sertraline and 17α-ethinylestradiol were investigated in a river that receives effluents from STP. The results indicate that the PhACs were extens...
Source: Ecotoxicology and Environmental Safety - February 21, 2018 Category: Environmental Health Authors: Liu J, Dan X, Lu G, Shen J, Wu D, Yan Z Tags: Ecotoxicol Environ Saf Source Type: research
Gemfibrozil and carbamazepine decrease steroid production in zebrafish testes (Danio rerio)
Publication date: Available online 10 February 2018 Source:Aquatic Toxicology Author(s): Shamaila Fraz, Abigail H. Lee, Joanna Y. Wilson Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical...
Source: Aquatic Toxicology - February 11, 2018 Category: Toxicology Source Type: research
Enhanced removal of PhACs in RBF supplemented with biofilm coated adsorbent barrier: Experimental and model studies
Publication date: 15 April 2018 Source:Chemical Engineering Journal, Volume 338 Author(s): Arya Vijayanandan, Ligy Philip, S. Murty Bhallamudi The present study focussed on potential application of river bank filtration (RBF) for the effective removal of pharmaceutically active compounds (PhACs), namely, atenolol, ciprofloxacin and gemfibrozil. Experiments on RBF were performed in a pilot scale reactor (3.0 m × 1.0 m × 0.5 m) in which two dimensional unconfined aquifer flow conditions were induced by pumping to depict realistic field conditions. Initially, experiments were carried out in a reactor fill...
Source: Chemical Engineering Journal - February 5, 2018 Category: Chemistry Source Type: research
Implications of inter ‐correlation between hepatic CYP3A4‐CYP2C8 enzymes for the evaluation of drug‐drug interactions: a case study with repaglinide
ConclusionsThe present study demonstrates via a systematic investigation that population‐based PBPK modelling incorporating inter‐correlation led to more consistent estimation of extreme values with those observed in inter‐individual variabilities of clearance and DDI. As the inter‐correlations more realistically reflect enzyme abundances, virtual population studies involving PBPK and DDI should avoid using Monte Carlo assignment of enzyme abundance. (Source: British Journal of Clinical Pharmacology)
Source: British Journal of Clinical Pharmacology - January 30, 2018 Category: Drugs & Pharmacology Authors: Kosuke Doki, Adam S. Darwich, Brahim Achour, Aleksi Tornio, Janne T. Backman, Amin Rostami ‐Hodjegan Tags: DRUG INTERACTIONS Source Type: research
Human UGT2B7 is the major isoform responsible for the glucuronidation of clopidogrel carboxylate
In this study, the glucuronidation of CCA was screened with pooled human liver microsomes (HLMs) and 7 human recombinant UGT (rUGT) isoforms. Results indicated that rUGT2B7 exhibited the highest catalytical activity for the CCA glucuronidation as measured with a mean Vmax value of 120.9 pmol/min/mg protein, 3‐ to 12‐fold higher than that of the other rUGT isoforms tested. According to relative activity factor approach, the relative contribution of rUGT2B7 to CCA glucuronidation was estimated to be 58.6%, with the minor contributions (3%) from rUGT1A6, rUGT1A9, and rUGT2B4. Moreover, the glucuronidation of CCA followed ...
Source: Biopharmaceutics and Drug Disposition - December 1, 2017 Category: Drugs & Pharmacology Authors: Jin ‐Zi Ji, Bei‐Bei Huang, Tong‐Tong Gu, Ting Tai, Huan Zhou, Yu‐Meng Jia, Qiong‐Yu Mi, Meng‐Ran Zhang, Hong‐Guang Xie Tags: ORIGINAL PAPER Source Type: research
Effects of gemfibrozil on the growth, reproduction, and energy stores of Daphnia magna in the presence of varying food concentrations.
Abstract
Gemfibrozil, a common lipid regulator, enters aquatic environments through treated municipal wastewater effluent that fails to remove it completely from effluent streams. When exposed to gemfibrozil concentrations of 50, 500, 5,000, and 50,000 ng L(-1), Daphnia magna showed increased lipid reserves by 14-21% (significant at 500 ng L(-1)), increased length by 9-13% (significant at 50 ng L(-1)), increased mass by 6-13% (significant at 50 ng L(-1)) and increased neonate production by 57-74% (significant at 50 ng L(-1)). Gemfibrozil-exposed Daphnia held under conditions where food availabili...
Source: Chemosphere - October 31, 2017 Category: Chemistry Authors: Steinkey D, Lari E, Woodman SG, Luong KH, Wong CS, Pyle GG Tags: Chemosphere Source Type: research
Assessment of gemfibrozil persistence in river water alone and in co-presence of naproxen
Publication date: January 2018 Source:Microchemical Journal, Volume 136 Author(s): P. Grenni, L. Patrolecco, N. Ademollo, M. Di Lenola, A. Barra Caracciolo Gemfibrozil is a pharmaceutical commonly found in the aquatic compartment and its presence together with a mixture of several other biologically-active drugs raises concern about the possible long-term adverse effects on biota chronically exposed. Most research focus on its effect/degradation in wastewater treatment plant, while few investigations take into account its persistence in receiving aquatic ecosystems and its effects on natural microbial communities. I...
Source: Microchemical Journal - September 28, 2017 Category: Chemistry Source Type: research
Utilizing PBPK Modeling to Evaluate the Potential of a Significant Drug-Drug Interaction Between Clopidogrel and Dasabuvir: A Scientific Perspective.
Abstract
Dasabuvir, a component of VIEKIRA PAK, is a substrate of CYP2C8 enzymes. Prescribing information for VIEKIRA PAK contraindicates gemfibrozil, a strong CYP2C8 inhibitor, because coadministration significantly increases dasabuvir exposures, which may increase the risk of QT prolongation. Clopidogrel may increase dasabuvir exposures primarily due to CYP2C8 inhibition by clopidogrel-acyl-β-D-glucuronide. This commentary outlines the US Food and Drug Administration (FDA) interdisciplinary review team's scientific perspective to address the potential for a significant drug-drug interaction (DDI) betwee...
Source: Clinical Pharmacology and Therapeutics - September 23, 2017 Category: Drugs & Pharmacology Authors: Arya V, Zhao P, Reynolds KS, Mishra P, Younis IR Tags: Clin Pharmacol Ther Source Type: research
Species ‐related exposure of phase II metabolite gemfibrozil 1‐O‐β‐glucuronide between human and mice: a net induction of mouse P450 activity was revealed
In this study, 6 volunteers were recruited and took therapeutic dose of gemfibrozil for 3 days for examination of the gemfibrozil and gem‐glu level in human. Male mice were fed a gemfibrozil diet (0.75%) for 7 days, following which a cocktail‐based inhibitory DDI experiment was performed. Plasma samples and liver tissues from mice were collected for analysis of gemfibrozil, gem‐glu concentration and cytochrome p450 enzyme (P450) induction analysis. In human, the molar ratio of gem‐glu/gemfibrozil was 15% and 10% at the trough concentration and the concentration at 1.5 h after the 6th dose. In contrast, this molar r...
Source: Biopharmaceutics and Drug Disposition - September 1, 2017 Category: Drugs & Pharmacology Authors: Min Luo, Manyun Dai, Hante Lin, Minzhu Xie, Jiao Lin, Aiming Liu, Julin Yang Tags: ORIGINAL PAPER Source Type: research
Effect of gemfibrozil and rifampicin on the pharmacokinetics of selexipag and its active metabolite in healthy subjects
ConclusionConcomitant administration of selexipag and strong inhibitors of CYP2C8 must be avoided, whereas when coadministered with inducers of CYP2C8, dose adjustments of selexipag should be envisaged. (Source: British Journal of Clinical Pharmacology)
Source: British Journal of Clinical Pharmacology - August 16, 2017 Category: Drugs & Pharmacology Authors: Shirin Bruderer, Marc Petersen ‐Sylla, Margaux Boehler, Tatiana Remeňová, Atef Halabi, Jasper Dingemanse Tags: DRUG INTERACTIONS Source Type: research
[Fibrates and risk of venous thromboembolism: Case/no-case study in French pharmacovigilance database].
CONCLUSION: With this study, we confirm the link between VTE and fenofibrate. It is therefore advisable to remain cautious when prescribing fenofibrate, in particular in case of past history of VTE and to declare systematically any venous thromboembolic adverse events observed with these drugs.
PMID: 28941579 [PubMed - as supplied by publisher] (Source: Therapie)
Source: Therapie - August 1, 2017 Category: Psychiatry & Psychology Authors: Humbert X, Dolladille C, Sassier M, Valnet-Rabier MB, Vial T, Guitton E, Page A, Sole E, Auriche P, Coquerel A, Alexandre J, Fedrizzi S Tags: Therapie Source Type: research
Effect of gemfibrozil or rifampicin on the pharmacokinetics of selexipag and its active metabolite in healthy subjects
ConclusionConcomitant administration of selexipag and strong inhibitors of CYP2C8 must be avoided whereas when co‐administered with inducers of CYP2C8 dose adjustments of selexipag should be envisaged. (Source: British Journal of Clinical Pharmacology)
Source: British Journal of Clinical Pharmacology - July 18, 2017 Category: Drugs & Pharmacology Authors: Shirin Bruderer, Marc Petersen ‐Sylla, Margaux Boehler, Tatiana Remeňová, Atef Halabi, Jasper Dingemanse Tags: DRUG INTERACTIONS Source Type: research
