title: A 14-day dose-response study of the efficacy, safety, and pharmacokinetics of the nonpeptidic protease inhibitor tipranavir in treatment-naive HIV-1-infected patients.
abstract: Tipranavir (TPV), a novel nonpeptidic protease inhibitor (NPPI), was administered to treatment-naive HIV-1-infected patients over 14 days in a randomized, multicenter, open-label, parallel-group trial to evaluate the efficacy and tolerability of a self-emulsifying drug delivery system (SEDDS) formulation, in combination with ritonavir (RTV). Of the 31 patients enrolled, 10 were randomized to receive TPV 1200 mg twice daily (TPV 1200), 10 patients received TPV 300 mg + RTV 200 mg twice daily (TPV/r 300/200), and 11 patients received TPV 1200 mg + RTV 200 mg twice daily (TPV/r 1200/200). The median baseline viral load and CD4 cell count were 4.96 log10 copies/mL and 244 cells/mm, respectively. After 14 days, the median decrease in viral load was -0.77 log10 in the TPV 1200 group, -1.43 log10 in the TPV/r 300/200 group, and -1.64 log10 in the TPV/r 1200/200 group. TPV exposure was increased by 24- and 70-fold in the TPV/r 300/200 and 1200/200 groups, respectively, compared with TPV 1200 alone. There were no significant differences across treatment arms with regard to drug-related adverse events. TPV/r appeared to be safe, effective, and well tolerated during 14 days of treatment.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA. smccalli@rdg.boehringer-ingelheim.com
authors.forename: Scott
authors.initials: S
authors.lastname: McCallister
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Kevin
authors.initials: K
authors.lastname: Curry
authors.forename: Thomas
authors.initials: T
authors.lastname: MacGregor
authors.forename: Marie
authors.initials: M
authors.lastname: Borin
authors.forename: William
authors.initials: W
authors.lastname: Freimuth
authors.forename: Yenyung
authors.initials: Y
authors.lastname: Wang
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mayers
mesh_terms: D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D015497:HIV-1; D006801:Humans; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D011753:Pyrones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage; D013449:Sulfonamides
chemical_list: D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; C107201:tipranavir