• Publications
  • Influence
The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors.
It is demonstrated that P-glycoprotein limits the oral bioavailability and penetration of these agents into the brain and raises the possibility that higher HIV-1 protease inhibitor concentrations may be obtained by targeted pharmacologic inhibition of P- glycoprotein transport activity. Expand
Drug metabolism and variability among patients in drug response.
  • G. Wilkinson
  • Medicine
  • The New England journal of medicine
  • 26 May 2005
This article focuses on the cytochrome P-450 enzymes, a superfamily of microsomal drug-metabolizing enzymes that play an important role in oxidative drug metabolism. Expand
OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine.
OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine's disposition and suggests potentially similar roles in the disposition of other xenobiotics. Expand
Identification of functionally variant MDR1 alleles among European Americans and African Americans
Allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P‐glycoprotein function. Expand
A physiological approach to hepatic drug clearance
The proposed classification of drug metabolism based on the hepatic extraction ratio allows prediction and interpretation of the effects of individual variations in drug‐metabolizing activity, route of administration, pharmacokinetic interactions, and disease states on hepatic drug elimination. Expand
Oral first‐pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A‐mediated metabolism
  • Kenneth E. Thummel, Diarmuid O'Shea, +4 authors G. Wilkinson
  • Chemistry, Medicine
  • Clinical pharmacology and therapeutics
  • 1 May 1996
To determine in humans the relative roles of intestinal and hepatic metabolism in the oral first‐pass elimination of a CYP3A substrate using midazolam as a model compound, data are presented on how these roles change over time. Expand
Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study
A CYP2B6 allelic variant that is more common in African-Americans than in Europeans-Americans was associated with significantly greater efavirenz plasma exposure during HIV therapy, and inter-individual differences in metabolism may, in part, explain susceptibility to efvirenz central nervous system side effects. Expand
The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans.
It is reported that the principal defect in poor metabolizers is a single base pair (G-->A) mutation in exon 5 of CYP2C19, which creates an aberrant splice site that results in a truncated, non-functional protein. Expand
Genetic variability in CYP3A5 and its possible consequences.
This review collates currently available data on CYP3A5 polymorphisms, provides information on the population frequency of each genetic variant in major ethnic groups, and describes in vitro and in vivo studies that have attempted to identify genotype-phenotype associations. Expand
Interrelationship Between Substrates and Inhibitors of Human CYP3A and P-Glycoprotein
The results indicate that the overlap in substrate specificities of CYP3A and P-gp appears to be fortuitous rather than indicative of a more fundamental relationship. Expand