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.

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The suppository for rectal administration of sodium valproate (VPA-Na) was prepared and its clinical effect was investigated in the epileptic patients to whom oral administration was difficult. We prepared two types of suppositories; type A included 600mg of VPA-Na, and type B included equivalent acetic acid in addition to 600mg of VPA-Na. VPA-Na contents in suppositories were determined using HPLC and plasma VPA concentration was determined by fluorescence polarization immunoassay.
The content of VPA-Na in type A suppository gradually decreased to 78% by 4 months when stored in refrigerator, whereas it remained unchanged in type B. When these suppositories were rectally administered to six volunteers, type A showed the mean peak plasma VPA concentration (Cmax) of 16.6μg/ ml and the area under the plasma concentration-time curve from 0 to 8h (AUC 0-8) of 107.6μg·h/ml, and type B showed Cmax of 47.7 μg/ ml and AUG 0-8 of 303.6μg·h/ml. The values of type B were significantly higher than those of type A. To three patients suffering from status epilepticus, type B suppositories were administered at doses of 600mg to 1, 200mg every 8hr, and to four postoperative patients, suppositories were administered at a dose of 600mg for prophylaxis against neurosurgical postoperative epileptic seizure in addition to oral administration of 600mg of VPA-Na. Status epilepticus was well controlled, although small amount of diazepam were also injected. In four patients who underwent neurosurgical operation, the plasma concentration of VPA was maintained within the therapeutic range, and no epileptic seizure was observed. The present study suggests that undissociated VPA suppository is effective for some epileptic patients.

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The use of a reagent for digoxin assay of fluorescence polarization immunoassay with TDX analyzer in the determination of serum deslanoside concentration was studied. Deslanoside calibrators with the concentration of 0.0-6.0 ng/ ml were prepared. The assay item for digitoxin was used for deslanoside after modification of the parameters. The coefficients of variation of within-run assay and between-run assay in this method were less than 9% at various concentrations tested. By use of a ultrafiltration method, the protein binding percent of deslanoside was determined to be zero or very small. In a patient with renal and hepatic failures, the half life (t_{1/ 2}) and the apparent volume of distribution (Vd) were calculated to be 131 hours and 4.1 1/ kg after intravenous administration of deslanoside, respectively.
On the other hand, an equation of Y= 1.25X+ 0.08 was obtained from a correlation between digoxin concentration (X) given by normal digoxin assay and concentration of deslanoside (Y). Therefore, with a simple method, one can calculate the deslanoside concentrations.

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Neutrophils play an essential role for the protection of bacterial infections by their phagocytic functions. Chemotherapeutics are also used for the same purpose. If these drugs impair neutrophil functions, the recovery from infections would be interfered. We found in vitro that ciprofloxacin (CPFX) inhibited the human neutrophil chemotaxis toward zymosan-activated serum, and that piperacillin (PIPC) enhanced the chemotaxis toward formyl-methionyl-leucylphenylalanine. It was a matter of our great interest whether these in vitro found functions could play roles for their clinical effectiveness or not. We surveyed data on white blood cells (WBC) and hemogram of the general as well as diabetic patients, candidates of immuno-compromised host, treated with either PIPC or CPFX. It was found that there were no serious changes of these data after long-term treatment with these drugs, although there were not so many cases with such data. We need further cases to discuss our final conclusions.

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The mechanism of diethylhexyl phthalate (DEHP) leaching from a polyvinyl chloride (PVC) container or an administration set into the intravenous alprostadil solution was investigated. After stored in the PVC bag for 24 hours at initial alprostadil concentration of 0.50μg/ ml, the released amount of DEHP was 20.5μg/ ml. The additives effecting on the DEHP leaching in the alprostadil injection were lecithin and soybean oil. It was estimated that DEHP leaching from the PVC membrane occurred through mechanisms of emulsification with lecithin and dissolution into soybean oil particle in the intravenous alprostadil solution.

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Patients who had undergone valve replacement were divided into 2 groups, the change-withtime group who had been treated with warfarin after the operation and in whom the coagulability had not reached the therapeutic range yet and the diurnal change group who had been treated with warfarin for more than 14 days and in whom the coagulability had been maintained in the therapeutic range. The relation between the coagulability, blood warfarin level, vitamin K level and coagulation factors were examined in these patients and the following became clear:
1) In the change-with-time group a close negative correlation was observed between theblood warfarin level and PT value or TT value. Hence, the blood warfarin level can be used as a parameter of coagulability at the initial stage of warfarin therapy. However, no negative correlation was observed between the two and the blood warfarin level cannot be a parameter of coagulability in the diurnal change group. 2) In the change-with-time group in whom about 3mg/ day of warfarin was administered, the blood warfarin level showed a value of 666ng/ ml on the 4 th day of administration when the PT and TT values tended to be maintained within the therapeutic ranges. The PIVKA (Protein Induced by Vitamin K absence or antagonists)-II (abnormal prothrombin which occurs due to vitamin K deficiency and which has no coagulable activity) showed a value of 7AU/ ml on the same day. Furthermore, a good correlation was obtained between the PT or TT value and PIVKA-11. Hence, PIVKA-J [is useful as a parameter to evaluate the anticoagulant effect of warfarin. 3) In the change-with-time group vitamin K₁-epoxide which is a metabolite of vitamin K₁ became measurable at the 11 th day and an increase in concentration was observed. A correlation with the blood warfarin level was observed. Accordingly, vitamin K₁-epoxide is useful as a parameter to evaluate the vitamin K cycle inhibition by warfarin. 4) In the change-with-time group protein C which has an anticoagulant effect showed the min. value of 0.72 μg/ ml on the 4 th day of warfarin administration. Protein C showed a good negative correlation with the blood warfarin level, PT and TT values, so that protein C is useful to evaluate the anticoagulant effect of warfarin. 5) Measurement of the blood level of warfarin, vitamin K1-epoxide, PIVKA-] I and protein C can be a clue to eluci date the poor maintenance of coagulability in the therapeutic range.

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Gliclazide is a hypoglicemic drug that highly binds to plasma proteins, but it is little reported about pharmacokinetics of free gliclazide which has a hypoglicemic action. In this study, we had an aim of establishing the HPLC method to measure free gliclazide and clarifying the effect of some diseases on it. Calibration curves were linear in the range of 0.2-10μg/ml (r=0.999). The limit of determination was 0.2μg/ml (C. V. 2.8%). Binding of gliclazide was not influenced by FFA under conditions employed and was dependent on bovin serum albumin (BSA) concentrations in vitro. In clinical, area under the curve (AUC) of free gliclazide of NIDDM with liver cirrhosis (n=3) was twice that of NIDDM without complication (n=8).(2.7±0.2 vs 1.3±0.2μg·hr/ml)

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The pharmacokinetics of phenobarbital (PB) was studied in 12 newborn infants following an acute i. v. and rectal administrations, respectively. In the 10 newborns whose gestational ages were 34 to 42 weeks and 2 infants whose ages were 6 and 13 months. The subjects were seizure or intraventricular hemorrhage or asphyxia at birth. PB pharmacokinetics was compared with single dose administration. The corresponding t_{1/ 2} for the i. v. dose was 103.4±65.5 hr (m±S. D.) and 138.06±100.1 hr (m±S. D.) after rectal administration. Maximum concentrations 10.25±3.4 μg/ ml (4.07-14.19 μg/ml) were reached between 5.68 and 30.13 hr after rectal administration. This variation in acute PB disposition for newborns is probably of limited clinical importance.

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An O/W type chlorophyll emulsion was prepared as a color marker to identify the lymph nodes. The emulsion consisted of chlorophyll oil, sesame oil, glycerin, water and surfactants. The final formulation containing 4% of phosphatidylcholine and 1.5% of polysorbate 80 as surfactants was stable over seven days at room temperature. The emulsion was endoscopically injected into the gastric submucosa of the dog. Laparotomy after two days of injection of emulsion showed that the lymph nodes have been stained green. Histological findings of the liver, kidneys, pancreas, lungs and heart of the rats did not show the toxic effect; one week after intraperitoneal injection of 2 ml/kg of the emulsion. Therefore, the chlorophyll emulsion was an effective and safe color marker to identify the lymph nodes from their surrounding tissues during the surgery of the malignancy.

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The effect of combined drugs (i. e. valproate, phenytoin) on serum levels of primidone (PRM) and phenobarbital (PB) derived from PRM and on the ratios of their serum levels to PRM dose (L/ D) were retrospectively evaluated in 37 epileptic patients. The L/D of derived PB and the PB/ PRM in serum levels were higher in patients taking PRM in both the combination with phenytoin (PHT) and with sodium valproate (VPA) compared to those taking PRM with other anticonvulsants. It was also demonstrated that the L/ D of PB and the PB/ PRM were affected by aging. The PB/ PRM in serum were significantly increased in group II (10≤X<20), III (20 ≤X<30) thangroup I (X<10).Furthermore, seasonalvariationsof the PB/PRM in 8 epileptic patients were evaluated. As a result, the PB/PRM in group A (during the period of April to September) were increased significantly (p<0.01), compared to that in group B (during the period of October to March).

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Instruction to patients about how to take medicines, so called “medicational instruction”, has become one of the most important work for hospital pharmacist. We made inquiries about the meaning of medicational instruction regarding to out-patients, nurses and physicians. As a result, the following matters were obtained. 1) There were many noncompliant patients about drug administrational owing to the lack of sufficient instruction by pharmacist. 2) Physicians and nurses recognize the meaning of the medicational instruction to patients by pharmacists.
Considering the results of the survey described above, we would like to make more sufficient medicational instruction to patients together with physicians and nurses.

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We established an easy and quick determination method of emetine (EM) and cephaeline (CP) in ipecac syrup by HPLC, which was carried out by using chloroquine as an internal standard. The calibration plots of these alkaloids showed a good linearity. Semi-preparative HPLC followed by mass-spectrometry was employed and the spectra of EM and CP isolated by preparative HPLC were found to be identical with those of authentic samples. Constant amounts of EM and CP were added to samples and the recovery rates were determined. This method gave a good recovery. The total contents of EM and CP in ipecac syrup from the USA ranged 153.2-184.9 mg/ 100ml and the content ratios (CP/ EM) were 2.6-3.0. These levels were higher than those of the USP standard for ipecac syrup.

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To study the cause for unreceived medicines, the relation between daily total numbers of prescriptions and unreceived medicines was investigated during October 1, to November 30, 1991. Numbers of the total prescriptions, unreceived medicines and final unreceived medicines were 43, 838, 297 and 19, respectively. Certain questionnaires and telephone contact trials against outpatients who did not receive the prescribed medicines were also performed. The questionnaires indicated that unreceived medicines which occurring in outpatients were caused by long waiting time for dispensing. Telephone contact trials reduced by approximately 70% numbers of final unreceived medicines, indicating that the trial is a means for reducing the unreceived medicines and noncompliance.

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A strain of Staphylococcus aureus was isolated from clinical material of an inpatient. The biological properties of the clinical isolate of S. aureus and its susceptibility to disinfectants and antibiotics were investigated. The clinical isolate of S. aureus was β-lactamase-positive and coagulase type-II strain, and the strain was found to produce penicillin-binding protein-2' and mec A gene, which are associated with bacterial resistance. Therefore, the clinical isolate was identified as the methicillin-resistant S. aureus (MRSA). Povidone-iodine was most rapidly bactericidal in vitro against the clinical isolate of S. aureus which was less susceptible to the other disinfectants. The clinical isolate of S. aureus was susceptible to OFLX and VCM. However, this strain was resistant to most of the antibiotics such as CMD, FOM or FMOX. In vitro antibacterial activity of the combinations of various antibiotics was evaluated by checkerboard dilution method. The fractional inhibitory concentration indices of FMOX+ CMD, FMOX+ FOM, FMOX+ FIPM, FOM+ FCMZ and F0M+ MINO were 0.51, 0.75, 0.63, 0.95 and 1.25, respectively. The effect of combination of FMOX+ CMD was superior to that of the other combinations against the clinical isolate of S. aureus. This finding suggests that combination therapy of FMOX and CMD may be useful for MRSA infections at the clinical dose.

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A simultaneous determination of four inorganic cations in cardioplegic solution was examined by indirect photometric ion chromatography (PIC). Cardioplegic solution was diluted 100-fold with 2.5mM copper sulfate aqueous solution, treated with SEP-PEK C₁₈ and ACCELL PLUS QMA cartridges, and then injected into the chromatograph. Large amounts of sodium, potassium and magnesium and small amount of calcium were separated on a Zorbax SCX-300 column with 2.5mM copper sulfate solution as an eluent, and detected as negative absorption peaks by an ultraviolet (UV) photometric detector at 230 nm. Straight calibration curves for the cations were obtained from 0.05 to 1.5mM by using a peak height ratio method. The reproducibility of the data was good enough. When cardioplegic solution was diluted 4-fold with the eluent, the determination of calcium in sample solutions was sufficiently good, in spite of over-loadings of the other cations on column. The results obtained by the PIC method were more accurate than those of the autoanalyzer meth

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