Impact of ABCB1 genotype in Collies on the pharmacokinetics of R- and S-fexofenadine.

摘要: Thirty-two Collies were used to determine the impact of ABCB1 genotype and phenotype on plasma pharmacokinetics fexofenadine's (Fex) R- S-enantiomers after bolus Fex administration, as human P-gp exhibits stereoselectivity. Each Collie's ivermectin (IVM) sensitivity (phenotype) was determined prior study enrolment. Wild-type (WT) had lower concentrations individual enantiomers compared heterozygous IVM nonsensitive (HNS), IVM-sensitive (HS) homozygous mutant (MUT) Collies. Based pairwise statistical comparison, WT statistically significantly (AUC0-last ) peak (Cmax values HS, HNS MUT Tmax not influenced by genotype/phenotype. Inter-individual variability in PK metrics tended be largest for Although influence genotype/phenotype occurred with isomers, impairment S-Fex absorption, particularly dogs, exceeded that associated R-Fex. Since elimination occurs primarily via biliary excretion a transporter other than P-glycoprotein, based upon our understanding absorption kinetics, we attributed these differences portion profile. These are expressed stereo-specific manner. results demonstrate potential negative estimates drug effectiveness toxicity, especially substrates do exhibit Central Nervous System toxicities.