ArticlePharmaceutical research2012
Prediction of nonlinear intestinal absorption of CYP3A4 and P-glycoprotein substrates from their in vitro Km values.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 49 citations in OpenAlex.
- Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in healthy adults.Antimicrobial agents and chemotherapy · 2015Trial
- Misconceptions among medicinal chemists regarding ADME and PK optimization.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Formulation Strategy of BCS-II Drugs by Coupling Mechanistic In-Vitro and Nonclinical In-Vivo Data with PBPK: Fundamentals of Absorption-Dissolution to Parameterization of Modelling and Simulation.AAPS PharmSciTech · 2025Review
- Evaluation of the Role of P-glycoprotein (P-gp)-Mediated Efflux in the Intestinal Absorption of Common Substrates with Elacridar, a P-gp Inhibitor, in Rats.European journal of drug metabolism and pharmacokinetics · 2020Article
- Impact of P-Glycoprotein on Intestinal Absorption of an Inhibitor of Apoptosis Protein Antagonist in Rats: Mechanisms of Nonlinear Pharmacokinetics and Food Effects.Pharmaceutical research · 2018Article
- Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions.Biopharmaceutics & drug disposition · 2017Review
- Projecting ADME Behavior and Drug-Drug Interactions in Early Discovery and Development: Application of the Extended Clearance Classification System.Pharmaceutical research · 2016Article
- Microdosing and drug development: past, present and future.Expert opinion on drug metabolism & toxicology · 2013Review
- Sucralose, a synthetic organochlorine sweetener: overview of biological issues.Journal of toxicology and environmental health. Part B, Critical reviews · 2013Review
- Minimizing Drug Exposure in the CNS while Maintaining Good Oral Absorption.ACS medicinal chemistry letters · 2012Article
- Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport.Pharmacology & therapeutics · 2012Review
- Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP.British journal of pharmacology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCYP3A4 and P-glycoprotein (P-gp) are present in the human intestine and mediate intestinal first-pass metabolism and the efflux of oral drugs, respectively. We aimed to predict whether intestinal CYP3A4/P-gp is saturated in a therapeutic dose range.
methodsInformation on the Michaelis-Menten constant (Km), product of the fraction absorbed (Fa) and intestinal availability (Fg) (FaFg) of CYP3A4/P-gp substrates, and clinical AUC data including two or more different dosages for each CYP3A4/P-gp substrate was collected. The relationship between dose-normalized AUC and dose/Km value, termed the linearity index (LIN), was analyzed.
resultsAmong 38 CYP3A4 and/or P-gp substrates, 16 substrates exhibited nonlinear pharmacokinetics and 22 substrates exhibited linear pharmacokinetics. Substrates with a small LIN tended to exhibit linear pharmacokinetics. The smallest LIN values of a substrate that exhibited nonlinear pharmacokinetics were 2.8 and 0.77 L for CYP3A4 and P-gp substrates, respectively. A decision tree for predicting nonlinear pharmacokinetics of CYP3A4/P-gp substrates based on LIN and FaFg of drugs was proposed. This decision tree correctly predicted linearity or nonlinearity for 24 of 29 drugs.
conclusionsLIN is useful for predicting CYP3A4/P-gp-mediated nonlinearity in intestinal absorption process in humans.
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