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Journal of Antimicrobial Chemotherapy 2005-Apr

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

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

Sleutelwoorden

Abstract

OBJECTIVE

We have investigated whether chemotherapy for HIV-related systemic non-Hodgkin's lymphoma (NHL) affects the pharmacokinetics of protease inhibitors.

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 AUC(0-8) 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 AUC(0-8) 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 C(0) and C(8) below the IC(50) 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.

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