title: Effects of the H2-receptor antagonist famotidine on the pharmacokinetics of atazanavir-ritonavir with or without tenofovir in HIV-infected patients.
abstract: Significant pharmacokinetic interactions can result between acid-suppressing agents and some protease inhibitors (PIs) in the management of HIV infection. In healthy subjects, famotidine, an H(2)-receptor antagonist, reduces exposures of atazanavir by 4-28% at doses of 20-40 mg twice daily. This study evaluated the effect of famotidine 20-40 mg twice daily on the pharmacokinetics of atazanavir/ritonavir 300/100 mg once daily with and without tenofovir disoproxil fumarate (TDF) 300 mg in HIV-infected patients (n=40; 87.5% male; mean age 42, range 26-63 years; 55% white). Coadministration of famotidine 40 mg and atazanavir/ritonavir to HIV-infected patients reduced exposures of atazanavir by approximately 20%. This is comparable to reductions seen in HIV-uninfected subjects. Coadministration of famotidine 20 mg had less impact on atazanavir exposures, with no reduction of atazanavir geometric mean plasma concentration at 24 h postdose (C(min)). In the presence of TDF, administration of famotidine 20-40 mg twice daily 2 h after and 10 h before atazanavir/ritonavir reduced exposures of atazanavir by 19-25%. However, all individual atazanavir C(min) values remained at least five-fold above the population mean protein-binding adjusted 90% maximum effect (EC(90)) against wild-type HIV (14 ng/mL). No viral load rebound was observed at end of study. The results confirmed that coadministration of an H(2)-receptor antagonist with atazanavir/ritonavir in HIV-infected patients resulted in similar magnitude of reductions in atazanavir exposures as in healthy subjects. This supports the current dose recommendations for coadministration of an H(2)-receptor antagonist with atazanavir/ritonavir.
authors.affiliation: Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhang
authors.forename: Ellen
authors.initials: E
authors.lastname: Chung
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Yaoshi
authors.initials: Y
authors.lastname: Wu
authors.forename: Kristine
authors.initials: K
authors.lastname: Patterson
authors.forename: Angela
authors.initials: A
authors.lastname: Kashuba
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Michael
authors.initials: M
authors.lastname: Child
authors.forename: Lisa
authors.initials: L
authors.lastname: Mahnke
authors.forename: Richard
authors.initials: R
authors.lastname: Bertz
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015738:Famotidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D006635:Histamine H2 Antagonists; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D000069446:Atazanavir Sulfate; D015738:Famotidine; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir