The purpose of the present study was to evaluate the pharmacokinetic interaction in rats between carvedilol and three kinds of dihydropyridine calcium-channel blockers, including nicaldipine hydrochloride, nifedipine and felodipine by high-performance inquid chromatography using a solid phase extraction column. The plasma crvedilol concentrations were found to be significantly higher than the control levels at 30 min-24 hr and 3-8 hr after the simultaneous administration of 20 mg/kg carvedilol and 40 mg/kg nicaldipine hydrochloride and 40 mg/kg nifedipine, respectively. In addition, the drug pharmacokinetic parameters, comprising the area under the concentration-time curve up to 24 hours (AUC_0-24), were 6.7 and 3.0 times higher after the administration of both carvedilol and nicaldipine hydrochloride and nifedipine, respectively. In contrast, after the administration of carvedilol and 5 mg/kg felodipine, the AUC_0-24 showed no change.
These changes are though to be attributable to either the vasodilator-induced changes in the hepatic first-pass metabolism or the metabolic inhibition.

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The pharmacokinetic interaction between carvedilol, a nonselective β-blocking agent and amlodipine besilate, a dihydropyridine calcium-channel blocker were investigated in rats. To determine the concentration-time profile of plasma carvedilol, blood samples were obtained from the tail vein after the oral administration of carvedilol either with or without amlodipine besilate. The plasma carvedilol concentrations and pharmacokinetic parameters, comprising the area under the concentration-time curve from 0 to 24 hours (AUC_0-24) showed no changes after the simultaneous oral administration of 20 mg/kg carvedilol and 5 mg/kg amlodipine besilate. In contrast, the plasma carvedilol concentrations at 6 hr-12 hr and AUC_0-24 after the oral administration of carvedilol with 40 mg/kg amlodipine besilate were significantly higher than those without amlodipine besilate.
These results suggested the pharmacokinetic interaction between carvedilol and amlodipine to be dependent on the dose of amlodipine.

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The oral bioavailability of such ionized drugs as ceftibuten, salicylic acid, and famotidine, when coadministered with enteral nutrition support was assessed in rats. Orally active nutrition support (HepanED^®, Twinline^®, Enterued^®) has exhibited an inhibitory effect on the absorption of ceftibuten from the rat intestine, thus suggesting this drug to not demonstrate the desired therapeutic effect. In Loop experiments using the rat intestine, the absorption rates of ceftibuten, salicylic acidand cimetidine were found to decreas to similar extents when combined withenteral feeding products. The suppression by such enteral feeding products is considered to be due to the interaction between the drug and the component (s) of the oral nutrition support, but is not thought to be related to the gastric emptying time. On the other hand, the absorption of levofloxacin, a zwitterionic compound, from the intestinal loop was not affected at all by HepanED^®. This result correlates with the previous date which showed no inhibitory effect of Enterued^® on cephalexin absorption. These findings therefore suggest a common relationship between the structures of the drug molecules and the inhibition behavior observed during enteral nutrition support.

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To clarify the present status of drug compliance in Japan and to help improve the administration appropriate drug therapy, we made an investigation of the literature regarding drug compliance in order to evalvate this problem.
We reviewed the literature related to the present status of drug compliance published between January 1994 and December 1996, using the on-line database of JMEDIC1N and the CD-ROM of the Medical Center Magazine.
The number of articles thus obtained totaled 30 and the number of the patients investigated amounted to 9710. The non-compliance rate in these 30 articles ranged from 23.1% to 61.5% with a mean of 32.2%. One of the reasons for such a wide variation was considered to be due to differences in the definition of the non-compliance. It has yet to be elucidated as to exactly what frequency of not taking drugs and what drug-remaining rate should be regarded as noncompliance. Regarding the reasons for non-compliance, a number of problems were cited such as “forgot to take drugs inadvertently” in which the patient is at fault, and “too many kinds of drugs to take” in which the drug therapy itself is considered to possibly be too complicated Therefore, when initially providing guidance regarding proper drug administration, it is essential to clearly make the patients understand the necessity of the drug therapy.

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A simple reverse-phase high-performance liquid chromatographic (HPLC) assay for the measurement of amiodarone and its metabolite, desethylamiodarone in the serum was established. The ODS-2 column was used and the absorbance of the effluent from the column at 254 nm was measured. The standard curves for amiodarone and desethylamiodarone were linear up to 5μg/ml. The coefficent of variation (CV) was within 10% at a concentration of 100 ng/ml, and the CV of the intra-and interday variation was within 10% at concentrations of 0.25, 0.5 and 1μg/ml, respectively. These results suggest that the limit of detection is 100 ng/ml for amiodarone and desethylamiodarone, and this assay is thus considered to be a reliable method in clinical practice. On the other hand, the serum amiodarone and desethylamiodarone concentrations were measured in 10 inpatients who received amiodarone for at least 1 month. No significant correlation was observed between the doses and serum drug concentrations. There findings therefore suggest that TDM (Therapeutic Drug Monitoring) should be performed on anyone taking amiodarone.

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We evaluated the inpatient-understanding of drug therapy and disease on admission. Based on the results of our survey, we designed a new type of medical diary in which inpatients could improve their knowledge of the relationship between drug therapy and disease. We distributed these medical diaries to inpatients, who were hospitalized with a vascular disease in the First Department of Surgery, Nagoya University School of Medicine. In addition, inpatient-understanding of drug therapy and disease was also evaluated based on three specific points which were determined at the initial and final inpatient consultation. The evaluation scores regarding the inpatient-understanding of drug therapy and disease increased from 0.72±0.56 to 1.6±0.50 (p<0.01) and from 1.4±0.51 to 1.8±0.37 (p<0.01), respectively.
These results suggest that the use of medical diary was helpful and allowed the patients to improve their overall understanding of both drug therapy and disease.

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We investigated the stability of Vitamins in a total parenteral nutrition (TPN) solution. We compared examinations at the same clinical site at two different dosage periods for the administration of Vitamins (daytime and nighttime) with the finding of a basic examination.
We thus found the stability in most instances to be the same as for the basic examination of stability in numerous Vitamins reports (effect of light and temperature, trace elements, sodium sulfite). At on clinical site during the different dosage periods, the dosage at nighttime was found to be better than that observed in the daytime. We consider this influence on stability of the Vitamins to be related to the alteration of the quantity of light during the daytime. These findings suggested that the addition of Vitamins to TPN solutions should therefore be avoided whenever possible during daytime administration.

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We conducted an anonymous questionnaire mail survey on patients, who had received medication instructions while hospitalized and were later discharged from the Department of Child Neurology from the first of October 1993 to the end of November 1995. The average age of the patients was 5.4 (0-21) years old, and the average frequency of medication instruction was 8.4 (1-46) times. The results of the overall evaluation from patients and/or their family to the medication instruction was “It was good” ; 92.3%, “Can not judge” ; 6.6%, and “It was bad” ; 1.1%, Moreover, it was “Necessary” ; 93.4%, “Not necessary” ; 1.1%, and “Can not judge” ; 5.5%. Regarding the question “Were the medication instructions sufficient?” “It was good” was 92.3% as an overall evaluation. Therefore, the medication instructions were generally considered to be good by the patients and/or their family. The results obtained from this survey were thus valuable in evaluating the medication instructions for child epilepsy patients.

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The compilation of a Problem List for certain problems regarding drug therapy obtained through a clinical pharmacy service is useful for detecting and preventing any adverse drug reactions or potential problems in clinical practice. Such useful information is not available many other pharmacists in Japan. We tried to develop a database and a software program for such a Problem List based on the pharmaceutical care records at our hospital according to our proposed format. This database consists of 771 data which can be cross-referenced to diseases, drug names and clinical divisions, respectively. Moreover, we can statistically evaluate the Drug Information contents by pharmacists using this database. We here in propose that all pharmacists in Japan carefully preserve their pharmaceutical care records based on our format and so that all may use the database jointly.

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A 61-year-old woman weighting 57.9 kg was hospitalized with deep vein thrombosis. She received warfarin therapy. At first 2 mg/day of warfarin was administered for five days while from the 6 th day the dose was increased to 3 mg/day. From the 8 th day the dose was increased to 4 mg/day. Although the GOT and GPT value was within the normal range before the warfarin therapy was started, on the 5 th day after the therapy was started the GOT and GPT levels were 68 and 61 Iu/l, respectively, while on the 12 th day the GOT and GPT had increased even more (99 and 212). We consider such hepatic evidence to be due to the administration of warfarin and its administration was thus stopped. On the 4 th day after warfarin was stopped the GOT and GPT levels decreased to 55 and 128, respectively, and after that it decreased even more. Both the GOT and GPT decreased to the normal range within one month. On the other hand, in order to evaluate an allergy to warfarin, a patch test of warfarin was examined, however, the results of the test was negative. No reports of hepatic failure due to the administration of warfarin could be found on Medline from 1966 to February 1998. These results suggest this case to be a very rare one, however, further study is called for in the future.

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An investigation of the use of a MDI (Metered-Dose Inhaler) of β-Stimulants or Steroids was carried out on bronchial asthmatic patients. The use of a MDI for the cure of bronchial asthma is standard. However, due to the misuse of these medicines, serious adverse-drug-reaction have also emerged and the importance of their proper use has thus gained attention. The patients understood the effect to be 95% for β-stimulants and 84% for steroids. The patients understood the proper use or dose to be 73% for β-stimulants and 62% for steroids. However, the patients who understood the effect of the medicines did not necessarily comprehend their proper use. Especially, the ratio of patients who used the medicine according to the doctor's instructions numbered 56% for β-stimulants and 53% for steroids.
These results suggest that it is important to supply the proper pharmaceutical instructions in order to use the MDI correctly for all patients.

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Pharmacists need to have a clear policy for managing investigational drugs under circumstances that are consistent with Good Clinical Practice. We studied the management and support system for the clinical research of investigational drugs based on the management of investigational drugs. We experienced 126 cases of pharmaceutical consultations in 650 prescriptions for investigational drugs from April 1997 to March 1998. Seven cases which might induce a patient to drop out, were included in pharmaceutical consultations. We found it was important to communicate with all investigators regarding giving adequate prior information to having a clearly defined protocol. Our pharmaceutical program for the clinical research of investigational drugs was thus found to be useful in the management of investigational drugs.

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The difference between the clinical pharmacy system in Japan and that in Australia is discussed. The clinical pharmacy systems at Australian educational hospitals, the Royal Melbourne Hospital, and the Monash Medical Centre were thus studied. Doctors in Australia prescribe drugs together with clinical pharmacists and therefore also pharmacists share responsibility with doctors. The promotion of efficient drug utilization is an important strategy at Australian hospital pharmacies. Such systems may be instructive for improving the overall clinical pharmacy services in Japan.

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We examined the changes in potency of polymyxin B sulfate (PL-B) solution on the following two factors, the concentrations of PL-B solution and sterilization methods of PL-B solution. The treatment with a filter (0.22μm) lowered the potency to 97-98% at concentrations of 1, 000, 3, 000 and 5, 000 units/mL of PL-B solutions immediately after filtration and the potency remained unchanged until 3 months. Treatments using an autoclave markedly lowered the potency to 70.0%, 76.6% and 84.0% at concentrations of 1, 000, 3, 000 and 5, 000 units/mL of PL-B solutions immediately after autoclaving at 115°C and 0.7 kg/cm² for 30 min, respectively. No subsequent decreases in the PL-B potency with sterilization by autoclaving were observed during the 3-month period.

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A computerized support system for checking prescriptions was developed in connection with the prescription order entry system already in operation at our institution. Drug interaction, drug duplication and contraindications for any prescriptions with overlapping administration periods can be checked by this system. The detected hazards are printed out on the prescription and the prescription-checking list on which medication histories are printed out. The pharmacist refers to the information from this system and then inspects the prescription. If the information from this system does not apply to the patient, the pharmacist can ignore this information. We established strict criteria for the prescriptions checking this system. In case that pharmacist suspects any potential problems and the physicians do not alter the prescription details, then the pharmacist registers such potential in this system. The registered information, which is printed on the prescription during the follow-up examination, prevents the pharmacist from continually finding the same problem.
After this system was introduced, the number of drug interactions and drug duplications decreased remarkably. we therefor find this system to be useful for the rational use of medication.

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