The pharmacokinetics of liposomal encapsulated daunorubicin are not modified by HAART in patients with HIV-associated Kaposi's sarcoma

Fumagalli, Luca; Zucchetti, Massimo; Parisi, Idria; Viganò, Maria Grazia; Zecca, Bruno; Careddu, Anna; D'Incalci, Maurizio; Lazzarin, Adriano
June 2000
Cancer Chemotherapy & Pharmacology;Jun2000, Vol. 45 Issue 6, p495
Academic Journal
Purpose: To investigate the pharmacokinetics of liposomal daunorubicin (DaunoXome) administered alone or in combination with antiviral therapy including protease inhibitors (PI) to HIV-positive patients affected by Kaposi's sarcoma (KS). Patients and methods: A group of 18 patients with extensive or rapidly progressing AIDS-related KS received DaunoXome at a dose of 40 mg/m2 alone or in association with a triple combination therapy consisting of one PI plus two nucleoside reverse transcriptase inhibitors (NRTI). Daunorubicin pharmacokinetics were determined in a total of 23 cycles, 6 with DaunoXome alone, 9 in combination with indinavir, 6 with ritonavir and 2 with saquinavir. Plasma samples were obtained at different times during the 72 h after DaunoXome administration. Daunorubicin and daunorubicinol plasma levels were determined by high-performance liquid chromatography. Results: After the DaunoXome infusion, daunorubicin was rapidly cleared from the body following, in most cases, a one-compartment open kinetic model. The daunorubicin peak concentrations, clearances and elimination half-lives were (means ± SD): 16.3 ± 2.8 μg/ml, 0.3 ± 0.1 l/h per m2 and 5.6 ± 2.6 h after DaunoXome alone; 15.1 ± 4.9 μg/ml, 0.5 ± 0.3 l/h per m2 and 5.8 ± 2.1 h after the combination with indinavir; and 14.5 ± 2.8 μg/ml, 0.4 ± 0.2 l/h per m2 and 6.5 ± 3.9 h after the combination with ritonavir. In all groups, daunorubicinol plasma levels were approximately 25–30 times lower than those of the parent drug. Conclusion: Our data show that there are no significant differences in the pharmacokinetic parameters of daunorubicin in patients receiving DaunoXome in combination with indinavir and ritonavir compared with those in patients not receiving PIs. Therefore in patients affected by AIDS-related KS treated with Highly Active AntiRetroviral Therapy (HAART) there is no pharmacokinetic justification for reducing the doses of DaunoXome.


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