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JAC Advance Access published online on February 22, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki050
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JAC © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Received September 21, 2004
Revised December 23, 2004
Accepted December 30, 2004

Original article

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

Mario Cruciani 1*, Giorgio Gatti 2 {dagger}, Emanuela Vaccher 3, Giampiero Di Gennaro 3, Roberta Cinelli 3, Matteo Bassetti 2, Umberto Tirelli 3, and Dante Bassetti 2

1 Centre of Preventive Medicine/HIV Outpatient Clinic, Via Germania 20, 37135 Verona, Italy
2 Department of Infectious Diseases, San Martino Hospital, University of Genoa, Genoa, Italy
3 Medical Oncology A, National Cancer Institute, Aviano, Italy

* To whom correspondence should be addressed.
Mario Cruciani, E-mail: crucianimario{at}virgilio.it


  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.

Keywords: indinavir; nelfinavir; CHOP; therapeutic drug monitoring.

{dagger}Current address. Vertex Pharmaceuticals, Cambridge, MA, USA.


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