Estimation of the Area under the Concentration-time Curve for Mycophenolic Acid Using Population Pharmacokinetics in Heart Transplantation Recipients

• Published in: Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) Vol. 45; no. 1; pp. 1 - 10
• Main Authors: Takayoshi, Maya, Wada, Kyoichi, Terada, Yuka, Takenaka, Hiromi, Matsuda, Sachi, Nishino, Ryoji, Miyazaki, Makoto, Nagai, Junya, Oita, Akira
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Pharmaceutical Health Care and Sciences 10.01.2019
• Subjects: heart transplantation; limited sampling strategy; mycophenolic acid; NONMEM; population pharmacokinetics
• ISSN: 1346-342X; 1882-1499
• DOI: 10.5649/jjphcs.45.1

The area under the concentration-time curve (AUC) of mycophenolic acid (MPA) in heart transplantation patients was estimated from a single plasma concentration using a population pharmacokinetic model as a substitute for the trapezoidal method that requires frequent sampling data. Plasma MPA concentrations at 2-12 h after oral administration were analyzed using a linear 1-compartment open model after intravenous injection. The individual pharmacokinetic parameters and plasma MPA concentrations were estimated from the observed single plasma MPA concentration based on the Bayesian approach. The AUC0-12h after oral administration was calculated by the trapezoidal method, using the predicted plasma MPA concentrations. The AUC0-12h value estimated from the plasma MPA concentration at 2 h after dosing adequately predicted the AUC value, calculated by frequent sampling data. These results indicate that the present estimation method for AUC0-12h is more convenient than the conventional method and is expected to be applied to clinical practice.