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Determination of low intrinsic clearance in vitro: the benefit of a novel internal standard in human hepatocyte incubations.
Xenobiotica
April 2019
a Global Early Development/Quantitative Pharmacology and Drug Disposition (QPD) , Biopharma, Merck , Darmstadt , Germany.
1. A novel method utilizing an internal standard in hepatocytes incubations has been developed and demonstrated to decrease the variability in the determination of intrinsic clearance (CL) in this system. The reduced variability was shown to allow differentiation of lower elimination rate constants from noise.
View Article and Find Full Text PDFDevelopment of an Enantioselective and Biomarker-Informed Translational Population Pharmacokinetic/Pharmacodynamic Model for Etodolac.
AAPS J
November 2017
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, 6550 Sanger Road, Orlando, Florida, 32827, USA.
Cyclooxygenase-2 (COX-2) isoform has a critical role in the development of pain. Inhibition of COX-2 in vitro serves as a biomarker for nonsteroidal anti-inflammatory drugs (NSAIDs). The NSAID concentrations yielding 80% COX-2 inhibition (IC) correlate with therapeutic doses to achieve analgesia across multiple COX-2 inhibitors.
View Article and Find Full Text PDFConcentration of non-steroidal anti-inflammatory drugs in the pelvic floor muscles: an experimental comparative rat model.
Yonsei Med J
July 2014
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
Purpose: The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model.
Materials And Methods: We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days.
Predicting the pharmacokinetics of acyl glucuronides and their parent compounds in disease states.
Curr Drug Metab
February 2006
School of Pharmacy, CB 7360, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Acyl glucuronides are potentially reactive intermediates, which not only undergo hydrolysis and intramolecular acyl migration, but also bind irreversibly to plasma protein in vitro and in vivo. To evaluate the impact of renal failure, liver dysfunction and other disease states on the pharmacokinetics of acyl glucuronides and their parent compounds, a pharmacokinetic model has been established. The model has been successfully utilized to predict the pharmacokinetics of six compounds, diflunisal (DF), valproic acid (VPA), zomepirac (Z), suprofen (S), R-etodolac (R-ET), S-etodolac (S-ET), and their acyl glucuronides in various simulated disease states in experimental animals.
View Article and Find Full Text PDFPharmacokinetic analysis of enterohepatic circulation of etodolac and effect of hepatic and renal injury on the pharmacokinetics.
Biol Pharm Bull
April 1997
Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
This study was designed to evaluate the enterohepatic circulation of racemic etodolac in rats. Additionally, the effect of hepatic and renal failure on the pharmacokinetics was estimated. The biliary excretion and the reabsorption of the drug excreted in bile were examined in order to clarify the effect of enterohepatic circulation on the disposition, and a pharmacokinetics model was applied to describe the enterohepatic circulation.
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