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Pharmacokinetic Interaction between Chemotherapy
for Non-Hodgkin's Lymphoma and Protease Inhibitors in HIV Patients
The
objective of the current study was to investigate whether chemotherapy for HIV-related systemic non-Hodgkin's
lymphoma (NHL) affects
the pharmacokinetics of protease
inhibitors.
This
was a prospective, open-label, non-randomized, two-way
crossover trial in HIV-1-infected patients treated with HAART and
chemotherapy for NHL.
Seven
patients received indinavir at a dosage of 800 mg three times
daily and three patients received nelfinavir (Viracept) 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
(Crixivan) 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
(Viracept).
· The
investigators 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 (TDM) of
protease inhibitors should be part of the work-up in
HIV-infected patients receiving chemotherapy for NHL.
Centre
of Preventive Medicine/HIV Outpatient Clinic, Via Germania 20, 37135
Verona; Department of Infectious Diseases, San Martino Hospital,
University of Genoa, Genoa; Medical Oncology A, National Cancer
Institute, Aviano, Italy.
06/24/05
Reference
M Cruciani and others. Pharmacokinetic interaction between chemotherapy for non-Hodgkin's lymphoma
and protease inhibitors in HIV-1-infected patients. Journal of
Antimicrobial Chemotherapy 55: 546-549. April 2005.
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