Toyohisa Tsukamoto

Dose adjustment of phenytoin for comedication in Japanese patients with epilepsy.

This study sought a suitable physiological parameter related to daily phenytoin (PHT) dose (D) providing a steady-state serum concentration (Ct) and analyzed the influences of coadministered antiepileptic drugs on Ct quantitatively to adjust PHT dose. Data were derived from a total of 368 patients with epilepsy treated with multiple oral administrations of PHT. Phenobarbital, carbamazepine, valproic acid, zonisamide, clonazepam, and ethosuximide were coadministered. For the administration of PHT alone, 4 types of parameter, that is, total body weight, total body water volume, body surface area, and extracellular water volume (VECW) were examined. Then, a Michaelis-Menten kinetic model was postulated including VECW, which was assumed to detect the effect of the coadministered drug quantitatively. Adopting VECW as a transforming factor, the concentration to dose (L:D) ratio [Ct/(D/VECW)] was independent of the patients age and gender in relation to Ct and expressed as Ct/(D/VECW) = 0.0245 × Ct + 0.076. Analysis clarified that ratios were estimated as 0.90, 0.91, 0.89, and 0.84 for phenobarbital, carbamazepine, valproic acid, and zonisamide, respectively, to maintain the same Ct concentration of PHT. Influences were not detected as the number (≧2) of coadministered drugs increased, regardless of factor type. PHT clearance changed in an age-dependent manner and was usually poorly correlated with weight-based doses. VECW was more closely correlated with age-dependent changes in physiological parameters such as clearance. VECW was considered to remove the influence of age on clearance, and estimated ratios could be used for all age groups. In the case of the addition or removal of concomitant treatment with antiepileptic drugs in the same patient, the daily PHT dose was calculated using the value of each ratio or its reciprocal. Our results could be helpful in determining PHT dosing.

Estimation of the Supporting Functions for Prescription Making in an Order Entry System.

In order to ensure that an order entry system for prescritions operates correctly and efficiently, we estimated the value of the supporting functions for prescription making. We examined the reports concerning the information supplied (e.g., drug name and directions), the functions of inspection prior to prescription making (e.g., usual dose and maximum dose), and the functions of inspection subsequent to prescription making (e.g., printing of the name of the diagnosis). In our hospital, rate of questions asked due to doubts about the prescription decreased from 4.2% to 0.6% since the order entry system was introduced. This decreasing factor of this asking rate was caused by “checking for an omission” (41%), “using information supplied” (37%), and conducting an “inspection prior to prescription making” (22%). The doctors and pharmacists concerned answered in the affirmative with regard to the supporting functions for the prescription making.We classified the prescription-making supporting functions into three levels on the basis of importance. In our classification, we concluded that the minimum required supporting functions (fundamental functions) for the preparing of a complete prescripton were “checking for an omission”, “information about the patient”, “drug name”, “selection of the drug”, “directions”, “ unit”, and “dose and times” . In addition, we summarized our standardization of the fundamental functions using the results of this examination.

Study of proper ordering quantity based on the forecast of drug demand.

Forecast of drug demand by computer needs the following parameters such as period of order, ordering point, ordering quantity and present stock.The regular order dates are Monday and Thursday, and the maximum lead time period is four days in our hospital.Ordering point, which is the sum of a minimum possession amount and a safety surplus amount, is set as the used amount of a drug in a week, theoretically.When ordering quantity is decided, the deferred stock should be considered.Therefore, we have investigated two cases;one case is to pull deferred stock from the predicted amount, another is not.The latter case got good results, when shortage probability, ordering quantity and frequency of order were compared. Next, the problem about the shortage of space occurred for the case of transfusions, which were of great bulk, when the ordering quantity was set as the accompanying used amount of a drug in two weeks.This problem was solved by changing the ordering quantity from the used amount of a drug in two weeks to the accompanying amount of a drug in certain period obtained from the real frequency of order in the previous year.