• Publications
  • Influence
Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance.
  • J. Houston
  • Biology, Medicine
  • Biochemical pharmacology
  • 29 April 1994
The Utility of in Vitro Cytochrome P450 Inhibition Data in the Prediction of Drug-Drug Interactions
TLDR
Findings support the conclusion that P450 in vitro inhibition data are valuable in designing clinical DDI study strategies and can be used to predict the magnitudes of DDI. Expand
Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity,
TLDR
This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro and how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes. Expand
Primary Hepatocytes: Current Understanding of the Regulation of Metabolic Enzymes and Transporter Proteins, and Pharmaceutical Practice for the Use of Hepatocytes in Metabolism, Enzyme Induction,
TLDR
This review brings you up-to-date with the hepatocyte research on in vitro–in vivo correlations of metabolism and clearance, the function and regulation of hepatic transporters and models used to elucidate their role in drug clearance, mechanisms and examples of idiosyncratic and intrinsic hepatotoxicity. Expand
BINDING OF DRUGS TO HEPATIC MICROSOMES: COMMENT AND ASSESSMENT OF CURRENT PREDICTION METHODOLOGY WITH RECOMMENDATION FOR IMPROVEMENT
TLDR
There is general agreement on the need to correct kinetic constants for the fraction of drug concentration unbound. Expand
In vitro-in vivo scaling of CYP kinetic data not consistent with the classical Michaelis-Menten model.
TLDR
This review critically examines these types of data, which require the adoption of an enzyme model with multiple sites showing cooperative binding for the drug substrate, and considers the constraints this kinetic behavior places on the prediction of in vivo pharmacokinetic characteristics, such as metabolic stability and inhibitory drug interaction potential. Expand
Human udp-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid.
TLDR
Diclofenac and probenecid inhibited all isoforms, precluding the use of these compounds for the reaction phenotyping of xenobiotic glucuronidation pathways in human tissues. Expand
Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver.
TLDR
The findings indicate the importance of considering differences between study populations when forecasting in vivo pharmacokinetic behaviour and recommend that the estimates (and their variances) from the current meta-analysis be used when predicting in vivo kinetic parameters from in vitro data. Expand
Prediction of Drug Clearance by Glucuronidation from in Vitro Data: Use of Combined Cytochrome P450 and UDP-Glucuronosyltransferase Cofactors in Alamethicin-Activated Human Liver Microsomes
TLDR
The applicability of combined cofactor conditions in the assessment of clearance for compounds with a differential contribution of P450 and UGT enzymes to their elimination is indicated, in particular for UGT2B7 substrates. Expand
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