Pharmacokinetic analysis was carried out with respect to the methotrexate (MTX) serum concentration. Nine patients (26 instillations) undergoing MTX therapy were investigated. Better correlation was shown between the MTX serum concentration and the dose per body surface area (BSA) as compared with the dose per body weight (BW) or the dose per ideal body weight (IBW).
Analysis of the data of the MTX serum concentration involved a 2-compartment open model (2-com) to determine four parameters (K₂₁, α, β and Vd) with respect to each instillation. As a result of the analysis, an extremely high correlation was observed between the calculated and the measured concentrations. To examine the effects of age and dose on the pharmacokinetic parameters, we divided the data into two groups: low-dose (<4000mg/m²) adult (≥15) group (LA group) and high-dose (≥4000mg/m²) child (<15) group (HC group).
Population pharmacokinetic parameters were calculated by standard two-stage (STS) method for the LA and HC groups, respectively. Significant differences were detected with respect to K₁₂, K₂₁ and β between the LA and HC groups. For an adult administered a high-dose of MTX, his/her parameters belonged to the values of the HC group. On the other hand, when a child was administered a low dose of MTX, his/her parameters belonged to the values of the LA group. Therefore, K₁₂, K₂₁ and β are considered to be determined only by the dose and not by the age.

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We have developed prolonged release preparations of amikacin and epirubicin using microfibrous collagen (Aviten^®) in combination with sodium alginate. The effect of sodium alginate on drug release from collagen was specially examined because an electrostatic interaction was expected bztween the carboxyl group of alginate and amino group of amikacin and epirubicin.
The release tests revealed that amikacin was rapidly released from the collagen, while its release was significantly delayed in the presence of sodium alginate in a concentration-dependent manner. Moreover, sodium alginate significantly retarded the release of epirubicin from collagen, despite the fact that epirubicin itself exhibited a strong affinity with collagen even in the absence of sodium alginate. Thus, it was shown that sodium alginate can be used to improve the controlled-release property of the microfibrous collagen preparation of certain drugs. Since the microfibrous collagen used is highly biocompatible, its preparations of amikacin and epirubicin with sodium alginate may be useful for local chemotherapy of bacterial infection and malignant tumor, respectively.

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We attempted to prepare diltiazem fast-release and fast-effect tablets using cellulose derivatives such as low-substituted hydroxypropylcellulose (LH-30 type L-HPC), hydroxyethylcelluose (CF-X type HEC, CF-G type HEC) and hydroxypropylmethylcellulose (TC-5E type HPMC) which are known as disintegrants and binders. The tablets were evaluated by in vitro dissolution test using the paddle method in JP XII second fluid (100 rpm, 37.0±0.5°C). The dissolution profiles showed that diltiazem was most rapidly dissolved from the tablet prepared with CF-G type HEC having four polymers. Moreover, the dissolution rate of diltiazem from the tablet prepared with CF-G type HEC was greater in the particle size of 106-250μm than in those of 53-106μm and 250-355μm. The effect of pH on absorption of diltiazem from the oral cavity was studied in six healthy volunteers. When diltiazem was administered to healthy volunteers with 0.1 M phosphate buffer solution, pH 7.0, the percent (25.5% of the dose) eliminated from the oral cavity was greater than that (6.9% of the dose) with 0.1 M phosphate buffer solution, pH 6.0 (p<0.01). From these results, it may be concluded that the formulation composed of diltiazem-HCl, CF-G type HEC with a particle size of 106-250μm and tribasic sodium phosphate is suitable for the oral cavity dosage form as the fast-release and fast-effect tablet.

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The pharmaceutical characteristics of Theodur (TD), Theolong (TL) and Slo-bid (SB) as commercial theophylline sustained-release preparations were investigated. According to the experimental design under the conditions consisted of temperature (20-80°C) and relative humidity (40-80%), these preparations were kept under five kinds of storage conditions for 14 days. The contents of theophylline in each of the preparations were stable. When preparations were kept at 80°-70%, the hardness of TD reduced rapidly with the passage of time. After keeping the preparation in 80° for 14 days, the release of theophylline from TD was accelerated. On the other hand, release of theophylline from TL was delayed with increasing temperature. SB was not suffered from temperature and relative humidity on the release of theophylline.
In the cases of TD and TL, the effect of the structural change on the release profiles was suggested by surface condition observation using a scanning electron microscope. Response variables were predicted by multiple regression analysis and simulation technique. The results reveald that each sustained release preparation designed by our pharmaceutical technique have different characteristics and produced a different effect on the drug release profiles according to the storage conditions.

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The relationship between the pharmacokinetics of Cyclosporine A (CyA) and the hepatic function was studied in a 15-year-old woman with hepatitis. At the early stage of treatment, the values of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total serum bilirubin (t-Bil) were higher than the normal range, suggesting hepatic cell injury and impaired bile formation and/or duct. The blood concentration ratio of CyA metabolites (Met) to CyA was markedly decreased from 1.92 to 0.74 in accordance with the clinical improvement in liver function. In addition a significant positive correlation was demonstrated between the Met/ CyA ratio and GOT (r=0.621, p<0.05), GPT (r=0.678, p<0.02) and t-Bil (r=0.824, p<0.001), while no significant correlation were found in the concentration-to-dosage ratio of CyA and Met. These results suggest the Met/CyA ratio could be a useful indicator for evaluate the clinical response and/or hepatic function. We would like to report this as a typical case that presented on apparent correlation of Met/CyA with liver functions. These results also indicate that the Met level as well as the unchanged CyA level should be evaluated in the hepatitis patient.

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We studied the effect of pharmacists drug consultation on the compliance of 239 inpatients (96 females, 143 males), who conformed to the condition of exceeding 14 days admission, being consulted over four times by pharmacists, and being able to manage the self-medication of prescribed drugs by six-objective assessment. Each assessment objective (1. setting of daily medication by self-administration, 2. medication, 3. interest in prescribed drugs, 4.understanding of prescribed drug's actions, 5. knowledge of relationship between disease and drug therapy, and 6. comprehension of adverse effects of prescibed drugs) was evaluated by three grades. The data between the initial and final of drug consultations were compared. The over-80-year-old group showed poor improvement in compliance even after drug consultation. And when patients take medication more than four times daily, the patients made more medication errors than did the others. There was an inverse relationship between compliance and the number of prescribed drugs. Significant improvements in the six objective assessments on drug therapy were observed in all other subjects at the time of discharge. These results indicated that the drug consultation by pharmacists could contribution to improving medication compliance.

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Conventional printed databases (or manuals) for drug information have unequivocal problems in adding new information, which are critical for drug safety, and in extracting required information from large amounts of data. Therefore, in this study, we developed a problem-solving system of drug information, named “MacDrug”, using HyperTalk on Macintosh personal computers. This system consists of major four functions; organizing various kinds of drug information, converting data sets from other databases, searching and extracting required information under any condition, and analyzing patient compatibility with drugs. All of these functions worked efficiently with the test data, and were shown to be useful in utilizing as much as possible the drug information. MacDrug can be localized in the public domain since the Hyper-Card program is bundled in every Macintosh computer with free of charge. Thus, we believe that MacDrug can help clinical pharmacists manage the advanced and complex drug information in an efficient manner.

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We compared a 7% lidocaine cream (Preparation C) prepared at our hospital using a commercially available 5% dental xylocaine ointment (Preparation K) for application as a lacal anesthesia for skin patients when employing a laser beam for stability and anesthetic performance. Both preparations did not show any water separation or color change at 5°C, 25°C, 40°C at RH 75% with a 95% or more residual rate. Furthermore, water evaporation in both preparations was not observed and was within the limit of measurement error. Significant change was not recognized in the expansibility of the preparation. The results of the viable cell count study according to Standard Plate-Counting Method and Specific Plate-Counting Method under the four conditions were negative (10 bacteria or less/g) with no observation of bacterial colonies. The anesthetic effect lasted 120 min for Preparation C with the 60-min application, while Preparation K only showed diminution of pain for 30 min.

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The pharmacist-examiner's business at the National Health Insurance Examination Committee of Medical Fees (NHIECMF) in Fukushima Prefecture is described. The most important business of pharmacist-examiner in the committee comprises two parts. One is examination of the pharmacist's fee claim forms and the issue of cautions, and the other is the explanation of various notifications concerning medicine at conferences attended by all examiners including doctors and dentists.
We recognize four problems concerning the pharmacist-examiner's role in NHIECMF system:
1) The number of pharmacist-examiner is so few that pharmacist-examiner can hardly contribute to safe and cost-effective use of medicines, 2) The pharmacist-examiner has no power to delete medical fees for unnecessary treatments, 3) The pharmacist-examiner cannot confirm whether the usage of medicines is suitable for the presented indications or not because there is no column describing patient's diseases in the phamacist's fee claim form, and 4) It is impossible for the pharmacist-examiner to check pharmaceutical management and counseling service.
It is therefore necessary for us to improve these problems immediately.

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Maternal milk volume safely given to the infant was estimated when the mother takes Phenobarbital (PB) or Phenytoin (PHT) or Valproic acid (VPA) or Carbamazepin (CBZ) or Theophylline (TP). To calculate the milk volume given to the infant, it was assumed that these drugs given to the mother and those transferring from maternal milk to the infant are at a steadystate and that the infant takes a constant volume of milk each time, every 6 hours, 4 times a day, and that the infant's body weight is 4 kg. The calculated milk volume by using the pharmacokinetic parameters of the infant and milk-to-plasma drug concentration ratio (M/P ratio) are respectively 65, 547, 589, 968, and 100ml/day when the infant's C_max a steady state which is less than 5% of maternal serum level is considered to be safe. This result indicates that maternal milk can be given to the infant safely when the mother takes CBZ and must not be given when the mother takes PB or TP and should be given to the infant carefully within the limits of permitted volume when the mother takes PHT or VPA since the infant is evaluated to take 600 to 840ml/day volume of milk.
TP secretion into breast milk was investigated. The measured M/P ratio was larger than the calculated M/P ratio according to pH-partitioing theory. This result suggests that some other factor influences TP secretion into breast milk to increase the M/P ratio.

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Influence of additives on friability, water absorption profiles and disintegration time of dried gel tablets prepared from gelatin-addedsodium citrate was investigated for preparation of dried gel tablets having high strength, fast water absorption rate and rapid disintegration as an oral preparation for elderly patients, pour kinds of Avice^® (PH101, PH301, PH-F20, RC-591NF), polyethylene glycol and poyvinylpyrrolidone were used as additives.
For the additives used friability decreased with an increase in the amount of additives. The apparent water absorption rate increased with the increase in the amount of PH301. Disintegration time was shortened at the mixing ratio of 15%(w/w) in PH301 and RC-951NF. These results suggested that the addition of 15% PH301 to dried gel powders is effective. In dried gel tablets to which PH301 was added at a mixing ratio of 15%, friability increased with the decrease in compression pressure but the apparent water absorption rate and disintegration time were scarcely affected by the compression pressure.

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To prescribe drugs or check a prescription, it is very important to understand the contraindications. We developed an original drug information system utilizing commercialy available application software. On the base of this system, we made a list of drugs sequenced due to each contraindication and a list of drugs contraindicated due to drug interactions for combination use. Thus, this list enables us to save times in our searching for the information.

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Simultaneous use of Kampo medicines ( “Gappo” ) has become fairly widespread through new prescription trials. Since there are little appropriate research data for simultaneous use, however it is difficult for pharmacists to check the prescription preparations. To obtain directly information on the safe use of Kampo medicine, we developed a Kampo medicine Gappo information database. The database information selected involved the overlapping of Kampo medicines compresing one of seven herbs: Glycyrrhizae radix, Rhei rhizoma, Rehmanniae radix, Ephedrae herba, Cinnamomi cortex, Aconiti tuber, or Gypsum fibrosum. The datebase with our previous three database, Kampo prescription preparation support database, Kampo medicine products information database, and a crude drug information database into a Unified Kampo Medicine Information Database System (UKMIDS).

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