The Effect Of Abcb1 Polymorphism On The Pharmacokinetics Of Saquinavir Alone And In Combination With Ritonavir

This genotype panel study investigated the effect of ABCB1 polymorphism in exon 26 ( C3435T), exon 21 ( G2677T/ A), and exon 12 ( C1236T) on saquinavir pharmacokinetics and on the expression and activity of P-glycoprotein ( P-gp) in peripheral blood monocytic cells ( PBMCs). One hundred and fifty healthy volunteers were genotyped to identify 15 TT3435 and 15 CC3435 individuals. In these individuals, saquinavir pharmacokinetics were assessed after administration of a single oral dose of saquinavir 1,000 mg and saquinavir/ritonavir 1,000/100mg. PBMC P-gp expression and activity were assessed in 15 and 19 subjects. The co-administration of ritonavir on study day 2 caused a significant increase in saquinavir exposure, in both TT3435 and CC3435 individuals. No correlation was observed between the ABCB1 C3435T, G2677T/ A, and C1236T polymorphisms, separately and in haplotypes, with saquinavir pharmacokinetics, administered with or without ritonavir and with PBMC P-gp expression and activity. In conclusion, ABCB1 polymorphism has no pronounced effect on saquinavir exposure.