title: Pharmacokinetic interaction between ritonavir and clarithromycin.
abstract: BACKGROUND
  Because ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, and clarithromycin, a macrolide antibiotic used in the treatment of disseminated infection caused by Mycobacterium avium complex, are likely to be administered concurrently for treatment of patients with HIV and acquired immunodeficiency syndrome (AIDS), the drug interaction potential of these 2 agents was evaluated. Both clarithromycin and ritonavir are metabolized to a significant extent through cytochrome P450-mediated biotransformation and are potential inhibitors of these enzymes.
  
  
  OBJECTIVE
  To evaluate the pharmacokinetic effects of concomitant administration of multiple doses of ritonavir and clarithromycin.
  
  
  METHODS
  This was an open-label, randomized, 3-period crossover study. Ritonavir alone (200 mg every 8 hours), clarithromycin alone (500 mg every 12 hours), and ritonavir and clarithromycin in combination were administered to 22 healthy volunteers. Blood samples were collected on day 4 for determination of ritonavir, clarithromycin, and its metabolite 14-(R)-hydroxyclarithromycin.
  
  
  RESULTS
  Ritonavir practically completely inhibited the formation of 14-(R)-hydroxyclarithromycin. The mean area under the plasma concentration-time curve (AUC) for clarithromycin increased by 77% with concomitant ritonavir, and the harmonic mean terminal half-life increased from 5 hours to 14 hours. Statistically significant increases in peak plasma concentration (31%) and minimum plasma concentration (182%) were also observed. The effect of concomitant clarithromycin administration on ritonavir pharmacokinetics was statistically significant but small, with a 12.5% increase in mean AUC and a 15.3% increase in peak plasma concentration. The terminal half-life increased from 3.47 to 3.87 hours with concomitant clarithromycin.
  
  
  CONCLUSIONS
  No adjustment of the ritonavir dose is necessary when administered with clarithromycin. In addition, no changes in clarithromycin dose are warranted in patients with normal renal function.
authors.affiliation: Abbott Laboratories, Abbott Park, Ill, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ouellet
authors.forename: A
authors.initials: A
authors.lastname: Hsu
authors.forename: G R
authors.initials: GR
authors.lastname: Granneman
authors.forename: G
authors.initials: G
authors.lastname: Carlson
authors.forename: J
authors.initials: J
authors.lastname: Cavanaugh
authors.forename: H
authors.initials: H
authors.lastname: Guenther
authors.forename: J M
authors.initials: JM
authors.lastname: Leonard
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017291:Clarithromycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008875:Middle Aged; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy; D012016:Reference Values; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D017320:HIV Protease Inhibitors; D017291:Clarithromycin; D019438:Ritonavir