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acetaminophen acid activity ADME studies administration aerosol analysis animal bile binding bioavailability bioequivalence Biopharm capsule chiral Chromatogr Clin clinical Cmax cokinetic column compared compounds concentration-time controlled-release product conventional-release curve dosage form drug absorption drug and metabolite drug concentration drug delivery drug metabolism drug product effect elimination enantiomers enterohepatic circulation enzyme Equation evaluation excretion FIGURE first-order first-pass gastrointestinal gastrointestinal tract glucuronide hepatic hepatocytes humans increase inhaled input intestinal intravenous intravenous dose intrinsic clearance J. G. Wagner kinetics linear liquid chromatography liver mass spectrometry Metab metabolite metabolite formation method Michaelis-Menten microcolumn oral dose pathways patients perfused Pharm pharmacokinetic model pharmacokinetic parameters pharmacokinetic studies Pharmacol phase physiological plasma concentration plasma levels population pharmacokinetic prodrug profiles protein radioactivity rat liver rate constant ratio renal robotic sampling simulation single-dose specific spectrometry steady-state substrate sulfation theophylline Ther therapeutic tissue toxicity transdermal values variability vivo Vmax volume of distribution