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Excerpt
Objective: The objective of this study was to evaluate the pharmacokinetic (PK) parameters of the protease inhibitor NFV and the new non-nucleoside reverse transcriptase inhibitor EFV in a group of HIV-positive patients (pts), in steady-state treatment with this antiretroviral combination regimen.
Methods: Heavily pretreated HIV-infected subjects, receiving a combination of NFV (750 mg every 8 hours), EFV (600 mg daily) and d4T (30-40mg twice daily), were considered for the PK evaluation. Plasma samples were obtained during a dosing interval (τ) for both drugs. NFV and EFV were quantified in plasma by specific and validated HPLC assays. NFV and EFV concentration-time data were analyzed by compartmental and non-compartmental tecniques (P-Pharm and Pharm-NCA Computer Program, Creteil, France).
Results: 20 pts were considered for NFV PK evaluation and 13 pts for EFV PK evaluation. We observed a large interindividual variability in PK parameters. Two pts with hepatic disfunction had abnormally elevated plasma levels of both drugs (3-4 times higher, with Cl/F values 50% lower) and were evaluated separately. Main PK parameters of NFV and EFV are reported in the following table (median and range).
Conclusions: The high variability in NFV PK suggests that there is great potential for using TDM to more precisely determine dosage for individual patients. Moreover, in pts with hepatocyte damage, dose reduction or extension of dosing interval may be required for both NFV and EFV.
