Hepatic Disposition and Metabolite Kinetics of a Homologous Series of Diflunisal Esters

1998 ◽  
Vol 87 (8) ◽  
pp. 943-951 ◽  
Author(s):  
Daniel Y. Hung ◽  
George D. Mellick ◽  
Yuri G. Anissimov ◽  
Michael Weiss ◽  
Michael S. Roberts
Keyword(s):  
Homologous Series ◽  
Metabolite Kinetics ◽  
Hepatic Disposition ◽  
Kinetics Of

Effect of adjuvant-induced systemic inflammation in rats on hepatic disposition kinetics of taurocholate

2011 ◽  
Vol 300 (1) ◽  
pp. G130-G136 ◽  
Author(s):  
Michael S. Roberts ◽  
Xin Liu ◽  
Yuhong Zou ◽  
Gerhard A. Siebert ◽  
Ping Chang ◽  
...  
Keyword(s):  
Bile Salt ◽  
Mrna Expression ◽  
Rate Constant ◽  
Systemic Inflammation ◽  
Atp Content ◽  
Influx Rate ◽  
Hepatic Disposition ◽  
Disposition Kinetics ◽  
Bile Salt Transporters ◽  
Kinetics Of

It has been reported that the adjuvant-induced inflammation could affect drug metabolism in liver. Here we further investigated the effect of inflammation on drug transport in liver using taurocholate as a model drug. The hepatic disposition kinetics of [3H]taurocholate in perfused normal and adjuvant-treated rat livers were investigated by the multiple indicator dilution technique and data were analyzed by a previously reported hepatobiliary taurocholate transport model. Real-time RT-PCR was also performed to determine the mRNA expression of liver bile salt transporters in normal and diseased livers. The uptake and biliary excretion of taurocholate were impaired in the adjuvant-treated rats as shown by decreased influx rate constant kin (0.65 ± 0.09 vs. 2.12 ± 0.30) and elimination rate constant kbe (0.09 ± 0.02 vs. 0.17 ± 0.04) compared with control rat group, whereas the efflux rate constant kout was greatly increased (0.07 ± 0.02 vs. 0.02 ± 0.01). The changes of mRNA expression of liver bile salt transporters were found in adjuvant-treated rats. Hepatic taurocholate extraction ratio in adjuvant-treated rats (0.86 ± 0.05, n = 6) was significantly reduced compared with 0.93 ± 0.05 ( n = 6) in normal rats. Hepatic extraction was well correlated with altered hepatic ATP content ( r2 = 0.90). In conclusion, systemic inflammation greatly affects hepatic ATP content/production and associated transporter activities and causes an impairment of transporter-mediated solute trafficking and pharmacokinetics.

Disposition and Metabolite Kinetics of Oral L-carnitine in Humans

2006 ◽  
Vol 46 (10) ◽  
pp. 1163-1170 ◽  
Author(s):  
Marcus A. Bain ◽  
Robert W. Milne ◽  
Allan M. Evans
Keyword(s):  
Metabolite Kinetics ◽  
Kinetics Of

Reactivation kinetics of a homologous series of bispyridinium bis-oximes with nerve agent-inhibited human acetylcholinesterase

2012 ◽  
Vol 86 (9) ◽  
pp. 1379-1386 ◽  
Author(s):  
Franz Worek ◽  
Jens von der Wellen ◽  
Kamil Musilek ◽  
Kamil Kuca ◽  
Horst Thiermann
Keyword(s):  
Homologous Series ◽  
Nerve Agent ◽  
Kinetics Of

Effect of cimetidine and phenobarbital on metabolite kinetics of omeprazole in rats

2005 ◽  
Vol 28 (10) ◽  
pp. 1196-1202 ◽  
Author(s):  
Eun-Ja Park ◽  
Hea-Young Cho ◽  
Yong-Bok Lee
Keyword(s):  
Metabolite Kinetics ◽  
Kinetics Of

scholarly journals Tacrine Sinusoidal Uptake and Biliary Excretion in Sandwich-Cultured Primary Rat Hepatocytes

2014 ◽  
Vol 17 (3) ◽  
pp. 427 ◽  
Author(s):  
Amal Kaddoumi ◽  
Loqman A. Mohamed
Keyword(s):  
Biliary Excretion ◽  
Rat Hepatocytes ◽  
Hepatic Uptake ◽  
Hepatic Transport ◽  
Glycoprotein P ◽  
Hepatic Disposition ◽  
Primary Rat Hepatocytes ◽  
Fold Reduction ◽  
Kinetics Of

PURPOSE. The knowledge of hepatic disposition kinetics of tacrine, a first cholinesterase inhibitor was approved by FDA for the treatment of Alzheimer’s disease (AD), would help to understand its hepatotoxicity, its therapeutic effect, and improve the management of patients with AD. The current study aims to characterize tacrine hepatic transport kinetics and study the role of organic cation transporters (OCTs), P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP2) in tacrine sinusoidal uptake and biliary excretion. METHODS. Modulation of tacrine hepatic uptake and efflux, biliary excretion index (BEI%), were performed in sandwich-cultured primary rat hepatocytes (SCHs) using transporters inhibitors. Conformation of the integrity of SCHs model was established by capturing images with light-contrast and fluorescence microscopy. RESULTS. Tacrine uptake in SCHs was carrier-mediated process and saturable with apparent Km of 31.5±9.6 µM and Vmax of 908±72 pmol/min/mg protein. Tetraethyl ammonium (TEA), cimetidine and verapamil significantly reduced tacrine uptake with more pronounced effect observed with verapamil which caused 3-fold reduction in tacrine uptake, indicating role for OCTs. Tacrine has a biliary excretion in SCHs with maximum BEI% value of 22.9±1.9% at 10 min of incubation. Addition of MK571 and valspodar decreased the BEI% of tacrine by 40 and 60% suggesting roles for canalicular MRP2 and P-gp, respectively. CONCLUSIONS. Our results show that in addition to metabolism, tacrine hepatic disposition is carrier-mediated process mediated by sinusoidal OCTs, and canalicular MRP2 and P-gp.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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