Pharmacokinetic interaction between chemotherapy for non-Hodgkin's lymphoma and protease inhibitors in HIV-1-infected patients

Mario Cruciani, Giorgio Gatti, Emanuela Vaccher, Giampiero Di Gennaro, Roberta Cinelli, Matteo Bassetti, Umberto Tirelli, Dante Bassetti

Research output: Contribution to journalArticle

Abstract

Objectives: We have investigated whether chemotherapy for HIV-related systemic non-Hodgkin's lymphoma (NHL) affects the pharmacokinetics of protease inhibitors. Patients and methods: This was a prospective, open-label, non-randomized, two-way crossover trial in HIV-1-infected patients treated with highly active antiretroviral therapy and chemotherapy for NHL. Seven patients received indinavir at a dosage of 800 mg three times daily and three patients received nelfinavir at a dosage of 750 mg three times daily. Chemotherapy consisted of adriamycin, cyclophosphamide, vincristine and prednisolone (CHOP). Each patient had blood samples for protease inhibitor pharmacokinetics drawn concomitantly with or independently of the CHOP cycle. Results: When indinavir was given concomitantly with CHOP, the AUC0-8 increased by 38% (20.5 ± 9.0 versus 14.9 ± 9.5 mg·h/L; P = 0.03), and was comparable to historical controls. By contrast, the AUC0-8 of indinavir administered without CHOP was lower than expected. A similar trend was observed with nelfinavir. Likewise, we observed a significant number of patients with C0 and C8 below the IC50 for the wild-type virus (0.1 mg/L) when the drug was administered without CHOP. Conclusions: Therapeutic drug monitoring of protease inhibitors should be part of the work-up in HIV-infected patients receiving chemotherapy for NHL.

Original languageEnglish
Pages (from-to)546-549
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume55
Issue number4
DOIs
Publication statusPublished - Apr 2005

Keywords

  • CHOP
  • Indinavir
  • Nelfinavir
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology

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