Pharmacokinetic interaction between chemotherapy for non-Hodgkin's lymphoma and protease inhibitors in HIV-1-infected patients.
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.
Cruciani
Mario
M
Centre of Preventive Medicine/HIV Outpatient Clinic, Via Germania 20, 37135 Verona, Italy. crucianimario@virgilio.it
Gatti
Giorgio
G
Vaccher
Emanuela
E
Di Gennaro
Giampiero
G
Cinelli
Roberta
R
Bassetti
Matteo
M
Tirelli
Umberto
U
Bassetti
Dante
D
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000097:blood / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003520:Cyclophosphamide / Q000097:blood / Q000494:pharmacology*; D004317:Doxorubicin / Q000097:blood / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000097:blood / Q000493:pharmacokinetics*; D011241:Prednisone / Q000097:blood / Q000494:pharmacology*; D011446:Prospective Studies; D014750:Vincristine / Q000097:blood / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D014750:Vincristine; D019469:Indinavir; D004317:Doxorubicin; D003520:Cyclophosphamide; D019888:Nelfinavir; D011241:Prednisone