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Pharmacokinetic Interaction Between Isavuconazole and a Fixed‐Dose Combination of Lopinavir 400 mg/Ritonavir 100 mg in Healthy Subjects
Author(s) -
Yamazaki Takao,
Desai Amit,
Han David,
Kato Kota,
Kowalski Donna,
Akhtar Shahzad,
Lademacher Christopher,
Kovanda Laura,
Townsend Robert
Publication year - 2016
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.282
Subject(s) - medicine , lopinavir , lopinavir/ritonavir , ritonavir , pharmacology , pharmacokinetics , human immunodeficiency virus (hiv) , virology , viral load , antiretroviral therapy
This phase 1, open‐label study evaluated the pharmacokinetic effects of coadministration of the antifungal agent, isavuconazole (administered as its water‐soluble prodrug isavuconazonium sulfate), with the antiretroviral agent lopinavir/ritonavir in healthy adults. In part 1, 13 subjects were randomized to 2 arms to receive multiple doses of oral isavuconazole 100 mg either alone or with lopinavir/ritonavir 400/100 mg. In part 2, a different group of 55 subjects were randomized to 3 arms to receive multiple doses of oral isavuconazole 200 mg, either alone or with lopinavir/ritonavir 400/100 mg, or to receive oral lopinavir/ritonavir 400/100 mg alone. Mean area under the concentration‐time curve (AUC) following the last dose (AUC τ ) and C max of isavuconazole increased by 113% and 96% in part 1 and by 96% and 74% in part 2 in the presence vs absence of lopinavir/ritonavir, respectively. Mean AUC τ and C max of lopinavir were 27% and 23% lower, and mean AUC τ and C max of ritonavir were 31% and 33% lower in the presence vs absence of isavuconazole, respectively. Mild to moderate gastrointestinal disorders were the most common adverse events experienced. These findings indicate that coadministration of lopinavir/ritonavir with isavuconazole can decrease the exposure of lopinavir/ritonavir and increase the exposure of isavuconazole. Patients should be monitored for reduced antiviral efficacy if these agents are coadministered.