Kazuhide Inoue

Clinical Application and Evaluation of Population Pharmacokinetic Parameters in Phenytoin Dosage Adjustment.

We investigated the influence and the usefulness of the population pharmacokinetic parameters (PPP) reported by Sheiner et al.[I], Grasera et al.[II], Miller et al.[III], IIIrd committee [IV] and Yukawa et al.[V], on the performance of the Bayesian feedback method in predicting the phenytoin (PHT) dosage.The predictabilites of the Bayesian feedback method using the data of 96 epileptic patients were evaluated. The mean prediction error and mean absolute predection error were applied for measures of prediction bias and precision. The precision of the initial estimates based on the PPP set [V] and [II] were superior to those baced on other parameters. Using the Bayesian feedback method the prediction values improved from the initial estimates were obtained regardless of the PPP sets used. The Bayesian feedback method seemed to give a prediction relatively insensitive to the population parameters used. We also found no inter-institutional differences in predicting the PHT dosage.

Effect of humidity on the stability of commercial soft capsule preparations of nifedipine.

Effects of humidity on the stability of nifedipine soft capsules were studied. Three commercial products were subjected to the test.Humidity conditions were set to be 55% and 80% of relative humidity and light resistant desiccators, where the samples were kept for 3 months under the same conditions as those previously reported. Changes of amount of both the contents of nifedipine soft capsules and nifedipine (Np) in the capsule shells were followed by high-performance liquid chromatography.Samples kept with PTP were stable, showing only slight decrease of the contents under both conditions. However, in the samples removed from PTP, it was observed that the amount of Np in the capsule shells increased with the decrease of the content and that Np oozed out the surface of the capsules at 80% of relative humidity. Differences of the amounts of Np which migrated from the content to the capsule shells were observed among the three products. It was also discussed that the migration was highly affected not only by the external environmental factors such as humidity but also by the factors of capsule preparations.

Influence of Hemolytic, Chylous and Icteric Factor on Serum Drug Level

In the measurement of a concentration of drug in serum by a method based on the enzymeantibody principle, the effects of serum factors such as hemolysis, chyle and icterus on the measured values were studied. Phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA) and digoxin (DGX) levels in serum were measured by the enzyme multiplied immunoassay technique (EMIT), and PB, PHT and CBZ levels by the substrate labeled fluorescence immunoassay (SLFIA).The effects somewhat varied by serum factors such as hemolysis, chyle and icterus, testing methods and drug; but as far as those 3 factors remain on the levels ordinarily observed, such effects on the measured values may be almost negligible. However, the DGX level rose more than 10% under the influence of bilirubin (5 mg/ dl).