Sparfloxacin (SPFX) is a long-acting new quinolone (NQ) due most probably to its enterohepatic circulation. We examined the drug interaction between sparfloxacin and the metal cation by measuring the urinary excretion of unmetabolized SPFX, and compared the findings with the interaction between norfloxacin (NFXL) and metal cations. The metal cations were found to be antacids containing aluminum and magnesium cations.
Urine samples for 12 hrs were collected for three days after the single oral administration of a 100-mg tablet of SPFX or norfloxacin (NFLX) in six healthy volunteers. The drugs were administered in the following four protocols: Control a single oral dose of. the NQ in the morning (A); a single oral dose of the NQ and the antacid simultaneously in the morning (B); a single dose of NQ followed by the antacid 3 times a day for 3 days starting 2 hrs after the NQ administration (C); and the oral dose of NQ and the antacid simultaneously in the morning and then the antacid 3 times a day for 3 days starting 2 hrs after the NQ administration. Urinary excretion of SPFX was still present at 72 hrs whereas that of NFXL was terminated within 24 hrs. The urinary excretion of SPFX for 72-hr period was in the order of Control>A=B>C, while that of NFLX was in the order of Control>B>A>C. In other words, the urinary excretion of SPFX or NFXL are markedly affected even when metal cations were administered 2 hrs after the NQ administration. The urinary excretion of SPFX continued to increase until 72 hrs after the administration in all protocols. Therefore, metal cations may interact with SPFX during the enterohepatic circulation, but it may not largely affect the urinary excretion of SPFX.

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To clarify the mechanism (s) contributing to the large interpatient variability in the dose of warfarin required for producing similar anticoagulant effects among cardiac patients, we performed; a) a retrospective medical chart survey to search for clinical variables associated with an interpatient variability of warfarin doses in 107 patients exhibiting stable anticoagulant effect during oral warfarin therapy administered constant doses of 0.5 to 7 mg; and b) a prospective clinical study in which steady-state total and unbound serum concentrations of warfarin enantiomers, determined with a newly developed chiral HPLC-UV detection method combined with an ultrafiltration technique, were correlated with the international normalized ratios (INRs) of prothrombin time in 8 patients given a chronic oral warfarin therapy. Results obtained from the medical chart survey showed that there was a 14-fold difference in the maintenance doses of warfarin among the patients and that the dose exhibited a significant age-dependent reduction (r=-0.26, p<0.01) Rirthermore, The clinical study revealed that while a significant correlation was observed neither between the warfarin doses and INR nor between the total serum concentrations of warfarin enantiomers and INR, there were significant (r>0.74, p<0.05) correlations between the unbound concentrations of both warfarin enantiomers and INR. These data suggest that the pharmacokinetic-dynamic relationship of warfarin should be analyzed based upon serum unbound enantiomer concentrations. It remains unclear whether S-warfarin possessing an anticoagulant effect 3 to 5 times more potent than its optical congener would have a greater contribution to the interpatient variability in the anticoagulant effects than that of R-warfarin.

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We investigated the relationship between the steady-state serum concentration of clonazepam and the daily dose per weight in epileptic children under 12 years of age who were receiving chronic monotherapy or polytherapy. We also examined the effects of the concurrent administration of other antiepileptic drugs, including phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), zonisamide (ZNS), and valproic acid (VPA), on the serum concentration of clonazepam by multiple linear regression analysis. The clonazepam concentration in the same daily dose and the concentration/dose ratio were lower in the polytherapy group than in the monotherapy group. The clonazepam concentration was noted to be positively proportional to the dose of clonazepam and was negatively affected by the addition of PB, PHT, and CBZ, but not of ZNS or VPA. The present results suggest that the differences of clonazepam pharmacokinetics in the monotherapy and polytherapy are associated with the effects of PB, PHT, and CBZ on the serum concentration of clonazepam.

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INGAI-SHOHOSEN (legal prescriptions for outpatients) has been insufficiently spread to community phamracies in spite of the Ministry of Welfares intention to promote of the IYAKUBUNGYO (separation of dispensing from medical practice) system. We consequently evaluated an organized effort to develop the conduct of IYAKU-BUNGYO system for distributing the prescriptions issued from Tottori University Hospital within the limits of the two neighboring prefectures of Tottori and Shimane.
We found that the Practice of issuing prescriptions is wide distribution for great many locations having community pharmacies. However, patients in the suburbs have been inconveniened because they must to utilize pharmacies located in the city of Yonago since there are no such facilities neer their residences.
Therefore, both hospital and community pharmacists are still desirous of making greater efforts to promote the a home pharmacy service to ensure a higher quality of life for outpatients.

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Investigation of the actual conditions and attitude surveillance of physicians to ward therapeutic drug monitoring (TDM) of theophylline were performed in outpatients prescribed a control released theophylline-tablet (Theodur ®) in November 1996. TDM of theophylline was performed in 1.6% of patients to whom were prescribed Theodur® during this period. The ratio of the patients who had a TDM history of theophylline was 28.1% of all patients prescribed Theodur®, while it was 41.7% in patients receiving over the usual Theodur® dose range (400 mg/day). Most physicians recognized the benefit of TDM, while about a half considered that TDM of theophylline is not essential for patients taking more than 400mg/day of the drug when their clinical condition is stable.

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In preparation for a study, we prepared a morphine suppository (MS-C suppository) that contained controlled-release morphine tablet (MS Contin^®) in the suppository base.
We then investigate plasma morphine concentrations and the analgesic effect produced following rectal MS-C suppository were investigated in three patients with cancer pain. Plasma morphine concentrations subsequent to this rectal administration were found to be much higher than those predicted from the morphine concentration administered orally.
The elimination half-life of morphine (t_1/2) after rectal administration was 2.5-4 times longer than that after oral administration of MS Contin^®. The clinically desirable analgesic effect was obtained in all patients tested. Though side effect of drowsiness was observed in two patients.
These results indicated that the MS-C suppository is a desirable treatment for ameliorating cancer pain.

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In outpatients with bronchial asthma, therapeutic events occurring before and after pharmaceutical instructions were investigated in patients having a better or poorer understanding their own disease and the medication being taken. No rehospitalization was observed in any of the patients after the pharmaceutical instructions were fully explained. The frequency of acute exacerbation required of intravenous drip of glucocorticoids and/or aminophylline were markedly decreased in a patients with a good understanding of the pharmaceutical instruction. In patients with a poor understanding, however, during the one-year period following the instructions, frequency of the exacerbations was almost the same as that before the instructions though exacerbation did not necessitate hospitalization and their clinical course improved afterwards. Our patients with bronchial asthma were able to comprehend the importance of medication with the partial improvement of symptoms resulting from carefully prescribed pharmaceutical instructions, especially with regard to the adequate use of the metered dose inhaler. Therefore, compared with the patients having other chronic diseases, patients with bronchial asthma took their medication with good compliance, along with adequate use of the metered dose inhaler despite some patients having a poor understanding of their disease and the efficacy of the medication administered.

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The methods for oral administration of the powdered antiepileptic drugs in 82 infant patients with epilepsy, who had been hospitalized in the Department of Child Neurology, were analyzed retrospectively for the 26 month term from the beginning of October 1993 to the end of December 1995. Of the antiepileptic drugs, sodium valproate (VPA) was prescribed the most. The powdered dosage form was the most frequently prescribed. Analysis of the method for taking pewders revealed the respective percentages of 36.6, 2.4, 4.9, 13.4, and 42.7%, for the ratio of suspension, jelly-like form, others, and intact. These results suggest that the dosage form is an important affecting the treatment of infant patients with epilepsy when prescribing antiepileptic medication is considered. Clearly essential is intensive research for developing a new dosage form of antiepileptic drugs for aiding in improving the quality of life of the child patients.

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We examined the drug interaction between zonisamide (ZNS) and carbamazepine (CBZ), valproic acid (VPA) or phenobarbital (PB) in 27 epileptic patients by monitoring the ratio of serum concentration at the steady state to the ZNS dose administered (C/D ratio). The C/D ratio ZNS therapy combined with CBZ was significantly decreased over that of ZNS monotherapy (p<0.01) whereas VPA or PB did not change the ZNS C/D ratio. Furthermore, the ZNS C/D ratio decreased with increasing the CBZ dose.
Accordingly, careful therapeutic drug monitoring should be done when administering ZNS concomitantly with CBZ.

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The superoxide anion scavenging activity of traditional Chinese medicines (Kampo) was estimated by the nitrate and nitrobluetetrazolium methods. No.15 and 34 revealed a strong superoxide anion scavenging activity and No.1, 7, 19, 25 and 45 revealed a relatively strong superoxide anion scavenging activity by nitrate method. On the other hand the nitrobluetetrazolium method revealed a relatively strong activity in No.1, 15, 25, 45 and 96. In particular, both methods denoted a relatively strong superoxide anion scavenging activity in No.1, 15, 25 and 45. These results suggest that the superoxide anion scavenging activity of each component accumulatively contribute to those Kampo medicines and might play an anti-inflamatory effect and “Ku-Oketsu” (improved blood circulation) effect in these medicines.

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A computerized support system for dispensing powder drugs was developed in connection with the prescription order entry system already in operation. This system incorporates three functions: verification of dispensing of powders, checking of refilling of powders into their stock bottles, and controlling powder dividing. During powder dispensing, the system is capable of collating the stock bottle powders with the prescribed powders, and of collating the amount of powders weighted by the pharmacist with that prescribed by the physician. When the name and amount of powders dispensed match those of the powders prescribed, the pharmacist can then dispense the next prescription. At refilling of powders into their respective stock bottles, the system which then permits the pharmacist to refill the stock bottle powders ensures the matching of the stock bottle with the original powder container. On dividing and packaging of powders using the powder divider, the system sets the diving number to powder divider, and the patient's name, prescription number and drug envelope number are printed on each unit-dose package. Checking this printed information enables the pharmacist to enclose correctly the unit-dose packages in their proper drug envelope. Since this on-line system facilitates all aspects of the powder dispensing process, we believe that it is particularly useful in preventing dispensing errors.

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Cytochromes P450 (P450) are known to be the enzymes responsible for the metabolism of most drugs. P450 data are thus important for the drugs clinical use since they are useful for predicting drug interactions and adverse side effects. From this point of view, we constructed a database including data obtained by in vitro methods using cDNA-expressed P450 and liver microsomes as well as data obtained by in vivo methods. the principal stored in vitro data are P450 forms, substrates and effects of inhibitors. The in vivo method data are administration methods, plasma concentrations of drugs, and DSST (digit symbol substitution test).
The data employed in this database were collected from the literatures, and the system was constructed using Access, Excel and Visual Basic 4.0 of Windows'95.

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Currently many hospitals employ their nurses to control the drugs being administered in each department, which has led to the problems of over-stocking and dead-stocking. In particular, because critical care medical center staff are exceptionally busy, there has been a remarkable loss of medical recept. Thus, in our effort to resolve this issue, pharmacy department have put our Supply Processing and Distribution System (SPD) into operation in our centers which makes possible the monistical control of keeping track of drugs and medical products in the hospital using a bar code pouch card. This has ensured that we have almost no loss of medical recept though there is an occasional misplacing of the BP card. However, the countermeasure we have enacted should lead to a good drug and medical product monitoring practice.

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