title: High indinavir Cmin is associated with higher toxicity in patients on indinavir-ritonavir 800/100 mg twice-daily regimen.
abstract: We retrospectively evaluated the incidence of side effects and treatment intervention according to indinavir trough concentration in 63 patients taking indinavir-ritonavir 800/100 mg twice daily. Median indinavir trough concentration was 1446 ng/mL at 800/100 mg twice daily associated with 60% of measured toxicity. Among patients with indinavir trough concentration >500 ng/mL, 46 of 49 had a dosage adjustment and 17 have had more than two dosage adjustments. The primary reason for dosage adjustment was toxicity in 69% (43 cases). Renal and cutaneous toxicity were predominant.After dosage adjustment, median indinavir trough concentration was 459 ng/mL, which was associated with 8% of toxicity. Trough concentrations >500 ng/mL were correlated with increased toxicity (p <.05) and more treatment intervention (p =.02). In conclusion, achievement of indinavir trough concentrations <500 ng/mL appears to be safe, and an optimal concentration range for indinavir trough concentration could be 150 to 500 ng/mL for an indinavir-ritonavir twice daily regimen.
authors.affiliation: Department of Pharmacokinetics, Timone Hospital, Marseille, France. caro_solas@yahoo.fr
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Basso
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ravaux
authors.forename: Hervé
authors.initials: H
authors.lastname: Gallais
authors.forename: Jean-Albert
authors.initials: JA
authors.lastname: Gastaut
authors.forename: Alain
authors.initials: A
authors.lastname: Durand
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012189:Retrospective Studies; D019438:Ritonavir / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D011480:Protease Inhibitors; D019469:Indinavir; D019438:Ritonavir