The pharmacokinetics of oral trazpiroben (TAK‐906) after organic anion transporting polypeptide 1B1/1B3 inhibition: A phase I, randomized study

• DOI: 10.1111/cts.13274
• Publication Date: 2022-04-23T08:31:54Z
• Authors: Jatinder K. Mukker; George Dukes; Max Tolkoff; Lisi Wang; Cristina Almansa; Susanna Y. Huh; Mitsuhiro Nishihara; Diane Ramsden; Chunlin Chen
• Keywords: Crossover study; Organic anion-transporting polypeptide

Trazpiroben is a dopamine D2 /D3 receptor antagonist under development for the treatment of gastroparesis. This phase I, open-label, randomized, two-way crossover study (NCT04121078) evaluated effect single-dose intravenous rifampin, potent inhibitor organic anion transporting polypeptides (OATPs) 1B1 and 1B3, on pharmacokinetics safety trazpiroben in healthy adults. The utility coproporphyrin (CP) I CPIII as biomarkers OATP inhibition was also assessed. Overall, 12 participants were enrolled randomized (1:1) into one two sequences (AB BA). Participants received either single oral dose 25 mg (treatment A) or immediately after 30-min infusion rifampin 600 B). After washout period at least 7 days, other treatment. Geometric mean area curve from time 0 extrapolated to infinity (AUC∞ ) maximum serum concentration (Cmax plasma higher receiving B than those A , 168.5 vs. 32.68 ng*h/ml; Cmax 89.62 14.37 ng/ml); corresponding geometric ratios (90% confidence interval) showed 5.16 (4.25-6.25) 6.24 (4.62-8.42)-fold increases these parameters, respectively. In this study, confirmed substrate OATP1B1/1B3, therefore co-administration with moderate strong inhibitors OATP1B1/1B3 not recommended. first assessment CPI endogenous rifampin.