Drug interactions on protein binding between phenytoin (PHT), valproic acid (VPA) and salicylic acid (SA) were studied by using human serum, when VPA and SA were added to serum concomitantly, percentage of unbound concentration (free percent) of both drugs were increased significantly than that of VPA or SA alone respectively. When PHT and VPA were added similarly, free percent of PHT was increased significantly than that of PHT alone, but that of VPA was not changed clealy. On the other hand, in the case of PHT and SA were added in the same way, free percent of both drugs were not changed significantly. The concomitant addition of PHT, VPT and SA to serum resulted in a significant increase of free percent of all the drugs compared to their respective controls and the degrees of their respective increases were similar to those that were shown by the concomitant addition of PHT and VPA or VPA and SA. From these results, it was considered that the concomitant clinical use of PHT, VPA and SA might strengthen the pharmacological effects of all these drugs.

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It is important that error of dividing weight of powder and/or granule of drugs by fullyautomatic dividing and packing machine is small. Effect of position of the division hole into which drugs begin to flow from feeder and number of total division holes on error of dividing weight was studied. The machine tested was OMP-90A (Tokyo Shokai), and 21g of CF-lactose used as a sample in this study was divided into 21 division holes. Weight of lactose in a packet calculated from that of each packet by total division method coincided with that observed by 21 division method, and coefficient of variation (C.V.) of dividing weight of the former was nearly equal to that of the latter. In the case of over 4 or more return motions of feeder, C.V. of dividing weight was not so much affected by position of the division holes. When powder of digoxin in a packet divided in the above condition was taken, the blood level was calculated from 1-compartment model by computer simulation. Effect of error of dividing weight on blood level of digoxin was small.

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