Impact of ritonavir dose and schedule on CYP3A inhibition and venetoclax clinical pharmacokinetics.
Autor: | Freise KJ; AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Hu B; AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA., Salem AH; AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA. ahmed.salem@abbvie.com.; Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. ahmed.salem@abbvie.com. |
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Jazyk: | angličtina |
Zdroj: | European journal of clinical pharmacology [Eur J Clin Pharmacol] 2018 Apr; Vol. 74 (4), pp. 413-421. Date of Electronic Publication: 2018 Jan 04. |
DOI: | 10.1007/s00228-017-2403-3 |
Abstrakt: | Purpose: Venetoclax is a selective BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). It is predominately metabolized by cytochrome P450 (CYP) 3A. The study objective was to determine the effect of different dosage regimens of ritonavir, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax in 20 healthy subjects. Methods: In cohorts 1 and 2, subjects received single 10 mg doses of venetoclax in periods 1 and 2 and a single 50- or 100-mg dose of ritonavir in period 2. In cohort 3, subjects received 10-mg venetoclax doses on day 1 of period 1 and days 1 and 11 of period 2, and 50 mg ritonavir daily on days 1 to 14 of period 2. Results: Single doses of 50 and 100 mg ritonavir increased the venetoclax maximum concentration (C Conclusion: After completion of the dose ramp-up, venetoclax dose reductions of at least 75% are recommended when administered concomitantly with strong CYP3A inhibitors to maintain venetoclax exposures within the established therapeutic window for CLL treatment. |
Databáze: | MEDLINE |
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