Related Experiment Video
Updated: Sep 26, 2025
![Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59557.jpg&w=3840&q=50)
Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941
Published on: April 28, 2019
The pharmacokinetics of oral trazpiroben (TAK-906) after organic anion transporting polypeptide 1B1/1B3 inhibition: A
Jatinder K Mukker1, George Dukes1,2, Max Tolkoff1
1Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA.
Abstract:
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 the effect of single-dose intravenous rifampin, a potent inhibitor of the organic anion transporting polypeptides (OATPs) 1B1 and 1B3, on the pharmacokinetics and safety of trazpiroben in healthy adults. The utility of coproporphyrin (CP) I and CPIII as biomarkers of OATP inhibition was also assessed. Overall, 12 participants were enrolled and randomized (1:1) into one of two treatment sequences (AB and BA). Participants received either a single oral dose of trazpiroben 25 mg (treatment A) or a single oral dose of trazpiroben 25 mg immediately after a single 30-min intravenous infusion of rifampin 600 mg (treatment B). After a washout period of at least 7 days, participants received the other treatment. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞ ) and maximum serum concentration (Cmax ) of plasma trazpiroben were higher in participants receiving treatment B than those receiving treatment A (AUC∞ , 168.5 vs. 32.68 ng*h/ml; Cmax , 89.62 vs. 14.37 ng/ml); corresponding geometric mean ratios (90% confidence interval) showed 5.16 (4.25-6.25) and 6.24 (4.62-8.42)-fold increases in these parameters, respectively. In this study, trazpiroben was confirmed as a substrate of OATP1B1/1B3, and therefore co-administration of trazpiroben with moderate to strong inhibitors of OATP1B1/1B3 is not recommended. This is also the first assessment of the utility of CPI and CPIII as endogenous biomarkers of OATP1B1/1B3 inhibition after a single intravenous dose of rifampin.
Related Concept Videos
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Factors Influencing Drug Absorption: Presystemic Elimination
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion,...
Drug Elimination by Renal Route: Tubular Secretion
Drug Biotransformation: Overview
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...

