Potential Drug-Drug Interactions with Combination Volasertib  + Itraconazole: A Phase I, Fixed-Sequence Study in Patients with Solid Tumors.

Potential Drug-Drug Interactions with Combination Volasertib + Itraconazole: A Phase I, Fixed-Sequence Study in Patients with Solid Tumors. Clin Ther. 2020 Oct 30;: Authors: Lang I, Liu D, Fritsch H, Taube T, Chizhikov E, Liptai B Abstract PURPOSE: This drug-drug interaction study determined whether the metabolism and distribution of the Polo-like kinase 1 inhibitor, volasertib, is affected by co-administration of the P-glycoprotein and cytochrome P-450 3A4 inhibitor, itraconazole. METHODS: This was an uncontrolled, open-label, fixed-sequence trial of two 21-day treatment cycles in patients with various solid tumors. In cycle 1 (test), eligible patients were administered volasertib (day 1) plus itraconazole (days -3 to 15). In cycle 2 (reference), patients received volasertib monotherapy. The primary end point was the influence of co-administration of itraconazole on the pharmacokinetic profile (AUC0-tz; Cmax) of volasertib and its main metabolite, CD 10899, compared with that of volasertib monotherapy. Other end points included tolerability and preliminary therapeutic efficacy. FINDINGS: Concurrent administration of itraconazole resulted in a slight reduction in the AUC0-tz (geometric mean ratio, 93.6%; 90% CI, 82.1%-106.8%) and a 20% reduction in Cmax (geometric mean ratio, 79.4%; 90% CI, 64.9%-97.1%) of volasertib compared with monotherapy. Of note, concurrent administration of itraconazole + volasertib had no ...
Source: Clinical Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Ther Source Type: research