Our mission is to promote medication therapy management that optimize therapeutic outcomes for individual patients.

The clinical pharmacologists (-kinetists) are charged with the obligation to quantify the dose-response relationship (pharmacokinetics and pharmacodynamics) of clinically useful drugs. Clinical pharmacokinetic studies are performed to determine the rational use of medicines according to patient characteristics, such as the disease and genotype of drug metabolizing enzymes (transporters), and to predict the influence of pharmacokinetic drug interactions.1,2)
We have recently proposed a new design/analysis approach for the patient-oriented clinical pharmacokinetic trial.1,3,4) The routinely treated patients often take drugs once daily or twice daily repetitively. The clinical practice-resembling pharmacokinetic trial may have less ethical problems, and its feasibility can be relatively high.1) We have performed the simulation for the exploratory clinical pharmacokinetic trial, in which blood is sampled at two time points corresponding to the peak and trough concentration following repetitive oral drug administration to 10-30 subjects.1,3) The simulation study indicated that the oral clearance (CL/F) value is estimated accurately by the naive trapezoidal method and/or by the simple mono-exponential model.1,3) Furthermore, we have been surprised that the pharmacokinetics of carvedilol in routinely treated patients with heart failure is significantly different from that in healthy subjects, and the precise mechanism has remained to be resolved.4)
Indeed, the pharmacokinetics of drugs in pediatric, elderly, and also middle-aged patients with disease is often and unexpectedly different from that in young healthy volunteers. We think that the pharmacokinetic evaluations for the patient population will be indispensable at least in the near future, and that we therefore can not help developing the limited sampling design and analysis method for each target drug.

References

1)Ishida, K., Kayano, Y., Taguchi, M., and Hashimoto, Y. : Simulation for clinical repeated-dose pharmacokinetic trials applying a peak-and-trough sampling designto estimate oral clearance. Biol. Pharm. Bull., 30 : 2159-2162 (2007).

2)Taguchi, M., Nozawa, T., Kameyama, T., Inoue, H., Takesono, C., Mizukami, A., and Hashimoto, Y. : Effect of CYP2D6*10 on pharmacokinetic variability of routinely a dministered metoprolol in middle-aged and elderly Japanese patients. Eur. J. Clin. Pharmacol., 59 : 385-388 (2003).

3)Takaai, M., Kayano, Y., Shimizu, T., Taguchi, M., and Hashimoto, Y. : Additional notes on clinical repeated-dose pharmacokinetic trials applying a peak-and-trough sampling design to estimate oral clearance. Drug Meab. Pharmacokinet., 23 : 128-133 (2008).

4)Horiuchi, I., Nozawa, T., Fujii, N., Inoue, H., Honda, M., Shimizu, T., Taguchi, M., and Hashimoto, Y. : Pharmacokinetics of R- and S-carvedilol in routinely treated Japanese patients with heart failure. Biol. Pharm. Bull., 31 : 976-980 (2008).