title: The effect of lopinavir/ritonavir and darunavir/ritonavir on the HIV integrase inhibitor S/GSK1349572 in healthy participants.
abstract: S/GSK1349572 is an unboosted, once-daily integrase inhibitor with a novel resistance profile. As standard of care for patients infected with HIV is combination therapy, the potential interaction between S/GSK1349572 and ritonavir-boosted protease inhibitors was evaluated. In an open-label, repeat-dose, 2-period, 2-sequence crossover study in healthy participants, S/GSK1349572 was administered at 30 mg once daily for 5 days, followed by randomization to lopinavir/ritonavir 400/100 mg twice daily or darunavir/ritonavir 600/100 mg twice daily coadministered with S/GSK1349572 30 mg once daily for 14 days. There was no washout between periods. Serial pharmacokinetic (PK) samples and safety assessments were obtained throughout the study. Thirty of 31 participants completed the study (15 participants per group). Treatment comparisons of steady-state S/GSK1349572 PK parameters demonstrated that coadministration of lopinavir/ritonavir had no significant effect on steady-state PK of S/GSK1349572. Coadministration of darunavir/ritonavir resulted in a nonclinically significant reduction in steady-state plasma S/GSK1349572 exposures. Plasma S/GSK1349572 AUC((0-τ)), C(max), and C(τ) decreased by 22%, 11%, and 38%, respectively, on average. S/GSK1349572 was well tolerated with no serious adverse events (AEs) or withdrawals due to drug-related AEs. The most frequent drug-related AEs were diarrhea, dizziness, and headache. No dosage adjustment for S/GSK1349572 is required when used with lopinavir/ritonavir or darunavir/ritonavir.
authors.affiliation: GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Ivy
authors.initials: I
authors.lastname: Song
authors.forename: Sherene S
authors.initials: SS
authors.lastname: Min
authors.forename: Julie
authors.initials: J
authors.lastname: Borland
authors.forename: Yu
authors.initials: Y
authors.lastname: Lou
authors.forename: Shuguang
authors.initials: S
authors.lastname: Chen
authors.forename: Parul
authors.initials: P
authors.lastname: Patel
authors.forename: Toru
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Piscitelli
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D000069454:Darunavir; D004338:Drug Combinations; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000494:pharmacology*; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; D019438:Ritonavir; D000069454:Darunavir