title: Time-dependent interaction between lopinavir/ritonavir and fexofenadine.
abstract: This study investigated the effect of single-dose and steady-state lopinavir/ritonavir on the exposure to fexofenadine, as a measure of P-glycoprotein activity. Sixteen volunteers (8 women) received single-dose oral fexofenadine 120 mg alone, in combination with single-dose ritonavir 100 mg or lopinavir/ritonavir 400/100 mg (randomized 1:1, stratified by sex), and in combination with steady-state lopinavir/ritonavir 400/100 mg twice daily. Single-dose ritonavir and lopinavir/ritonavir increased the area under the fexofenadine plasma concentration-time curve from 0 to infinity (AUC(infinity)) by 2.2- and 4.0-fold, respectively (P < .02). Steady-state lopinavir/ritonavir increased the fexofenadine AUC(infinity) by 2.9-fold. No changes were observed in the fexofenadine elimination half-life (P > .12). The fexofenadine AUC(infinity) was increased by lopinavir/ritonavir, likely due to increased bioavailability secondary to P-glycoprotein inhibition. After repeated administration of lopinavir/ritonavir, the interaction was attenuated compared to the single-dose effect, although a net inhibitory effect was maintained. Time-dependent inhibition of P-glycoprotein by lopinavir/ritonavir should be considered when P-glycoprotein substrates are coadministered.
authors.affiliation: Ottawa Hospital, Divisio of Infectious Diseaeses, Canada. rvheesw1@tibbe.jnj.com
authors.forename: Rolf P G
authors.initials: RP
authors.lastname: van Heeswijk
authors.forename: Marc
authors.initials: M
authors.lastname: Bourbeau
authors.forename: Pearl
authors.initials: P
authors.lastname: Campbell
authors.forename: Isabelle
authors.initials: I
authors.lastname: Seguin
authors.forename: Bobby M
authors.initials: BM
authors.lastname: Chauhan
authors.forename: Brian C
authors.initials: BC
authors.lastname: Foster
authors.forename: D William
authors.initials: DW
authors.lastname: Cameron
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D011744:Pyrimidinones / Q000493:pharmacokinetics / Q000494:pharmacology*; D019438:Ritonavir / Q000493:pharmacokinetics / Q000494:pharmacology*; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D006634:Histamine H1 Antagonists; D027361:Organic Anion Transporters; D011744:Pyrimidinones; D061466:Lopinavir; D016593:Terfenadine; C093230:fexofenadine; D019438:Ritonavir