The need to use xenobiotics to quantify liver function is based on the fact that the serum levels of endogenous tracers (such as transaminases, alkaline phosphatase, bilirubin and bile acids) cannot be interpreted in pharmacokinetic terms, since information is lacking on volume of distribution and on rate of synthesis and of disposition. Methods are now available which allow practically non-invasive estimation of (minimal) hepatic perfusion by indocyanine green fractional clearance, of portosystemic shunt flow by finger pulse photometry following nitroglycerin administration, of microsomal capacity by the aminopyrine breath test (ABT) or caffeine clearance, and of cytosolic function by galactose elimination capacity (GEC). Assessment of inherited hydroxylation deficiency of the debrisoquine type is best performed with dextromethorphan, and of the acetylator phenotype with sulfadimidine. Recently, caffeine clearance in saliva has been studied extensively in this laboratory, and, on the basis of a constant relationship between caffeine concentrations in serum and saliva, overnight clearance measurements (requiring a saliva sample at bedtime and upon arising following a single oral dose of caffeine) have been shown to be closely related to ABT or GEC. This approach, which has been successfully used in children, may represent the first simple and innocuous test for quantifying of hepatic function in the pediatric age group. The clinical utility of these clearance tests is to assess severity of disease (or genetically determined impairment of function), thus yielding important clues to prognosis.
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Nutrients
December 2024
Laboratory of Genetics of Aging and Longevity, Kazan State Medical University, 420012 Kazan, Russia.
Background: The monocarboxylate transporter 1 (MCT1) plays a crucial role in regulating lactate and pyruvate transport across cell membranes, which is essential for energy metabolism during exercise. The A1470T (rs1049434) polymorphism has been suggested to influence lactate transport, with the T (major) allele associated with greater transport efficiency. This study aimed to investigate the effect of the polymorphism on lactate and potassium (K) concentrations in response to resistance exercise (RE) following caffeine (CAF) ingestion.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Cleveland Diagnostics, 3615 Superior Ave., Cleveland, OH, 44114, USA. Electronic address:
The partition coefficient of human serum albumin (HSA) was analyzed in the PEG600-Dex70, 0.15 M NaCl/KCl in 0.01 M Na/K phosphate buffer, pH 7.
View Article and Find Full Text PDFAm J Emerg Med
December 2024
Department of Critical Care Medicine and Trauma, National Hospital Organization Disaster Medical Center, Japan.
J Clin Pharmacol
September 2024
Certara UK Limited, Simcyp Division, Sheffield, UK.
Vatiquinone, a 15-lipoxygenase inhibitor, is in development for patients with Friedreich's ataxia. Physiologically based pharmacokinetic (PBPK) modeling addressed drug-drug interaction gaps without additional studies. A PBPK model (Simcyp Simulator version 21, full model) was developed using parameters obtained from in vitro studies, in silico estimation and optimization, and two clinical studies.
View Article and Find Full Text PDFTarget Oncol
November 2024
Janssen Research & Development, Spring House, PA, USA.
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