Both the pharmaceutical evaluation and clinical utilization of vancomycin ointment have been investigated in the topical treatment of methicillin-resistant staphylococcus aureus (MRSA) infection. An ointment containing 2.5% of vancomycin hydrochloride was prepared using a base consisting of white petrolatum and liquid paraffin. The spreadability was 324 dyn/cm² at 25±2°C and 65±5% RH. The particle sizes of vancomycin hydrochloride in the ointment were distributed within 10-30μm. Vancomycin hydrochloride was stable for 4 weeks at 5, 20 and 40°C. The ointment was topically applied to the infectious region of a artificial bone graft. The treatment with the vancomycin ointment was found to be effective against MRSA infection. Since no substantial distribution was observed in the blood, the effect was also shown to be regionally restricted. In addition, no appearance of vancomycin resistance after using the ointment has yet been observed in this patient.
These above findings thus indicate that vancomycin ointment is effective, useful and safe for the treatment of topical MRSA infection.

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The effects of prednisolone (PSL) on physiological factors, i. e. plasma lipids and blood proteins regulating cyclosporin A (CsA) blood distribution were evaluated in renal transplant patients. The clinical data of 46 blood samples from 10 outpatients with a stable renal function, who received CsA and low dose PSL (10 mg/day), were thus analyzed. The PSL concentration in plasma (C_PSL) showed a significant positive correlation with hematocrit (HCT) and total cholesterol (CHO) but not with any other clinical laboratory tests related to either protein or lipid metabolism. In a multiple regression analysis the contribution that selected variables made to the CsA trough level was as follows: CHO > HCT >dose of CsA >C_PSL. This finding suggests that the drug-interaction between PSL and CsA was much due more to either the changes in the physiological factors regulating the CsA blood distribution via protein anabolism or the unusual lipid metabolism of PSL than dut to the enzyme-inducing action of PSL for CsA. Taking the PSL concentration in plasma and the effects of PSL on protein or lipid metabolism into consideration, it is thus possible to optimize the effect of immunosuppressive therapy in renal transplant patients.

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We developed a prolonged-action oxybutynin hydrochloride (OB) solution (5 mg/10 ml) for intravesical instillation therapy in the treatment of refractory urinary incontinence in neuropathic bladder disease. Hydroxypropylcellulose (HPC) was selected as a viscosifying agent. The OB solution containing HPC (HPC-OB solution) exhibited Newtonian viscosity. Although the release of OB from the HPC-OB solution was retarded by an increase in the HPC concentration, the apparent release rate constant was scarcely affected by solutions with more than a 1.0% HPC. Based on these findings, the optimal concentration of HPC was thus selected to be 1% in pharmaceuticals as a viscosifying agent. The pH of the HPC-OB solution containing 1% HPC was 5.94 and was stable for 6 months under all storage conditions. OB was stable under cold-dark conditions for 6 months. However, the residual content of OB was 94.8 and 95.1% after 6 months storage at room temperature under light and dark conditions, respectively.
The urine concentrations of OB after a single intravesical instillation of OB (5 mg/10 ml) were also evaluated. The amount of urine excretion of OB after HPC-OB solution was significantly lower than that after OB solution at first urination. The total amount of urine excretion of OB after HPC-OB solution thus appeared to be low compared with that after OB solution. These results thus suggest that OB may remain intravesically after the instillation of HPC-OB solution for a longer period than that of OB solution.
In conclusion, based on the above findings the use of intravesical HPC-OB solution is thus considered to be a more practical procedure than the use of OB solution for controlling incontinence in neuropathic bladder disease.

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When phenytoin fine granules and diluted digoxin powder are mixed with diluents, an especially high uniformity of mixing is required in clinical practice. In the present study, a quantitative analysis was performed to evaluate of mixing properties of either phenytoin fine granules or diluted digoxin powder, using fine lactose and corn starch as the diluents (mixing ratio, 7: 3). Twenty grams each of phenytoin and the diluents was put into a mortar without sieving and then was mixed in a spiral manner with a pestle, while the mortar was fixed with the left hand on the dispensing table (method A) or the pastle was moved in the opposite direction (method B). At least 80 times of the mixing was required in method A to obtain a permissible limit of good mixing (less than 6.08% as the coefficients of variation (CV) of phenytoin), while only 60 times was required in the method B. In addition, the effect of sieving on the degree of mixing was also investigated. When 20 g each of digoxin and diluents was mixed by method B, the CV was more than 12% even after 80 times of mixing. However, when digoxin and the diluents were mixed after sieving (32 mesh, 500μm), the CV of digoxin decreased drastically and a permissible limit of good mixing was obtained at 60 times of mixing. These differences in the mixing efficiency with and without sieving could thus be explained by electron microscopic observations. On the other hand, in the case of phenytoin, sieving had scarcely any effect.
Based on these results, in the case of phenytoin, at least 60 times of mixing with a pestle accompanied with the round movement of the mortar is required. On the other hand, in the case of digoxin which requires a high degree of mixing, the similar mixing after sieving is required.

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The effects of coadministrated antiepileptics; carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), valproic acid (VA), primidone (PD), on the serum zonisamide (ZNS) concentration were investigated. Routine therapeutic drug monitoring data, obtained from 98 epileptic patients who were treated by an oral administration of ZNS, and consisting of 287 serum concentration data at steady-state, were collected. Each ratio (L/D) of the serum level (L) to the daily dose per body weight (D) was used for the analysis.
First, the mean values of the L/D ratio of ZNS alone and each coadministrated antiepileptic were calculated. As the values of the ratio obtained from dividing each mean value by that of ZNS alone indicated the degrees of effect on the L/D ratio of ZNS alone, these values are thus considered to be the variation ratios of each coadministrated antiepileptic. Next, all the data were analyzed by the non-linear model under the assumptions that the effect of each coadministrated antiepileptic on the L/D ratio of ZNS alone is independent and multiplicative.(L/D) _{ZNS (0)} is 3.89, and the variation ratios of CBZ, PB, PHT, VA, PD, are estimated as 0.98, 0.90, 0.83, 0.71, 0.77, respectively. The (L/D) _{ZNS (0)} means have no effects on the coadministrated antiepileptics to the L/D ratio of ZNS.(L/D) _{ZNS (0)} was nearly equal to the mean of the L/D ratio of ZNS alone and each variation ratio was also nearly the same as that calculated in the manner described above. These findings thus support the above assumptions that the effect of each coadministrated antiepileptic on the serum ZNS concentration is independent and multiplicative.
These variation ratios thus calculated by the non-linear model seemed to be useful indicators for predicting serum ZNS concentration changed in the case of the addition or discontinuance of coadministrated antiepileptics for the treatment of ZNS in epileptic patients.

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A lipid emulsion containing PGE₁ within its lipid particles (Lipo-PGE₁) is expected to repected PGE₁ gradually from the lipid particles in clinical application. In medical practice, Lipo-PGE₁ is generally applied after being diluted with infusion fluids. PGE₁ is thus thought to be released rapidly from the lipid particles to the aqueous phase when Lipo PGE₁ is diluted with infusion fluids. We have kinetically studied the release of PGE₁ from both the Lipo-PGE₁ and PGE₁ solution as a control, while varying both the quantity of the diluting fluid and the temperature. We kinetically simulated the release of PGE₁ from the lipid particles of Lipo-PGE₁. As a result, that Lipo-PGE₁ was thus suggested to release PGE1 from the lipid particles rapidly after dilution.

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We measured the plasma levels of acetaminophen (AAP) and gastrointestinal peptides (motilin, vasoactive intestinal peptide, and β-endorphin) during a gastric emptying test performed on a 64-year-old male patient with progressive autonomic failure and five healthy volunteers. Subjects received 200 ml of a test meal containing 1500 mg of AAP after an overnight fast. The plasma levels of AAP for the first 90 min and the AUC_0→45minwere lower in the patient than in the normal subjects. The patient's levels of gastrointestinal peptides were also outside the normal ranges. These results demonstrated that the patient had delayed gastric emptying and that his gastric symptoms were thus predominantly due to parasympathetic disorders. After two-week therapy with cisapride, the AAP level increased and the levels of gastrointestinal peptides became normal or near-normal, thus suggesting cisapride to be effective in patients with progressive autonomic failure. These findings suggest that the monitoring of gastric emptying and the measurement of the gastrointestinal peptide levels were found to be useful for assessing the gastric function and for identifying the underlying mechanism of pathological conditions.

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The dissolution characteristics of two sustained-release preparations widely used in Japan, one taken twice-a-day (Theodur^® tablet) and one taken once-a-day (Uniphy^® tablet), were examined.
Both preparations showed a near zero order release and the rates were almost equal in pH 1.2, but a deifference was observed in the two preparations regarding pH 6.8. When influences due to halving of the tablets and changes in the rotative number of the basket were examined in pH 6.8, the Uniphyl^® tablet was found to be less influenced than the Theodur^® tablet.
The maintenance time of the effective concentration of these two preparations was predicted based on the absorption profiles in six volunteers and the elimination of several diseases on reference. Although the Uniphyl^® tablet showed a remarkable susutained-release effect, the time to peak (T_max) tended to appear early and the maximum concentration (C_max, ) was significantly lower than that of the Theodur^® tablet. However, there was no difference in the area under the salivary concentration curve up to infinity time.
If circadian rhythms are not taken into consideration, the administration of either a Theodur^® or Uniphyl^® tablet once-a-day should fully prevent a morning dip even in cases of enhanced elimination such as in hyperthyroid patients. On the other hand, for cirrhosis patients, these results suggest that even tablets normally taken twice-a-day can be taken once-a-day for Round The Clock (RTC) therapy.

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We conducted a survey to evaluate a system adopted by the Pharmacy Department of Tokyo University Hospital to address the problem of drug compliance under this system, patients are provided with a “Drug History Handbook”, or drug notebook. This survey attempted to determine the extent to which a “Drug History Handbook” helped patients understand the drug they were taking, and the extent to which it was utilized during visits to other institutions. Based on the results of the survey, we evaluated the efficacy of “Drug History Handbook” as a means to enable patients themselves to perform comprehensive drug information management.
Out of 288 patients responding to the survey, 149 (52%) had a “Drug History Handbook” 149 out of 286 respondents or 40% had been diagnosed at other institutions. The respondents who said they had shown their “Drug History Handbook” to pharmacists or physicians at other pharmacies, hospitals, or medical institutions were numbered 71 out of 149 (48%), including duplicate responses.
At community pharmacies conducted at the same time, responses were obtained from 48 pharmacies. Of the 48 responding pharmacies, 21 (44%) said that patients had presented either “Drug History Handbook” or “prescription cards” .
From these results, it is clear that the patients thus realized the importance of keeping a complete record of the drugs they had taken, and that presenting information about drug history can be a very valuable aid in both prescribing and preparing appropriate medications.
From thus survey, it was found that the use of a “Drug History Handbook” can help prevent the dispersal of information about purchase of over the counter drugs as well as prescription drugs. As a means of patient education, it can also be extremely effective for avoiding the duplicated administration of medications and drug-drug interactions.

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The fungicidal activity of acidic electrolyzed water (Aqua oxidizing water, AQ) and nine commercial disinfectants was studied using three methods of contact on two kinds of pathogenic yeast and two kinds of conidia.
In a glass test tube, with a ratio of I to 9 of Fungal suspension 10⁷ cfu/ml water to AQ, the fungi were killed by AQ within one minute, but the same amount of AQ was not effective against fungi suspended in a medium of Sabouraud dextrose broth (SDB). The killing activity of 50 ppm sodium hypochlorite (CL), which included the same amount of chlorine as AQ, was weaker than that of AQ and was also inhibited by SDB. The killing activities of 3% hydrogen peroxide, 500 ppm CL, 1% chloramine T (CT) and 0.5% chlorhexidine gluconate were weaker than that of AQ, but were not inhibited by SDB.
On a stainless steel tray, the fungicidal activity was weaker than the activity observed in the glass tube. After a 30-minute exposure, AQ killed both kinds of yeast completely, but neither type of conidia.
Organic substances influenced the fungicidal activity of AQ. On an agar plate or in the glass tube with proteins, the killing activity of both AQ and 50 ppm CL was inhibired. The influence of CT, a kind of chloric oxidizer, varied according to the pH of the substances.
AQ therefore shows a more potent fungicidal activity than ordinary chloric oxidizers with less chlorine because of its acidity, but is inhibited by organic substances to the same extent as CL which includes the same amount of chlorine. In conclusion, AQ is thus considered to be useful in washing and rinsing the surface of materials for the purpose of sterilization.

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A fully automated enzyme immunoassay system, Omni (BIO-TEK Co.) (ELISA system), using Markit-M Excegran and Markit-M Haloperidol (Dainippon Pharmaceutical Co.) was evaluated to determine the concentrations of zonisamide (ZNS) and haloperidol (HP) in human plasma. At first, the within-run (ZNS: n=8, HP: n=10) and the between-run (4 days) precisions of ZNS and HP were examined.
The coefficient of the variations in both the within-run and the between-run precisions of HP were below 5.0 and 7.0%, respectively. In contrast, the some values of ZNS were below 6.5 and 8.4%, respectively. A good correlation was observed between this ELISA system and HPLC (r=0.917), which was used to determine the plasma ZNS concentration. In the case of HP, a good correlation was seen between this ELISA system and the manual ELISA method (r=0.978).
This method was thus used to monitor the serum levels in patients receiving ZNS or HP therapy. The relationship was observed between the daily dose (mg/kg) and the plasma concentration of the trough level for ZNS and HP, respectively (r=0.750 p<0.001, r=0.669 p<0.001). However, the ratio of the plasma concentration of ZNS and the daily dose increased significantly with aging.

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We previously developed a HyperText-based program, MacAdvice, to efficiently prepare compliance-instruction sheets for prescribed drugs. In this study, we made a questionnaire survey which was given to both nurses and in-patients to objectively evaluate the program. The results showed that almost all nurses and patients found the instruction-sheets produced by MacAdvice to be useful, and that 91% of the patients became more concerned with their drugs after receiving the instruction sheets together with oral guidance. Moreover, we also observed a marked improvement in the patients' drug compliance after we started to use the MacAdvice program.

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Caffeine-containing agar-jelly was considered as a therapy for a patient suffering from severe headache and serious tremors on the upper extremites. However, no reliable information on the release of caffeine from agar was obtainable from a literatur-search. The present study was focused on examining the intactness of caffeine in jelly, the extent of release of caffeine from jelly and the assurance of its bacteria free condition.
Caffeine (50mg) was embedded in 15 ml agar-jelly. The jellies were either kept at room temperature (25°C) or stored in refrigerator (4°C) for a maximum of 7 days, depending on the experiments. The jellies were disintegrated in either the first disintegration test fl uid (pH 1.2) or the second disintegration test fluid (pH 6.8) at 37°C by a mechanical stirring. The extent of dissociation and the recovery of caffeine were then examined by HPLC. Bacterial contamination was examined by a culture.
The preparation of caffeine-containing agar-jelly was simple and easy to use. The intrajelly distribution of caffeine was superb. The release was rapid and plateaued to nearly 100% before 60 min in the two disintegration test fluids. The release took place before its disintegration proceeded. Neither the quantity nor the quality of caffeine was affected by the storage length. In addition no bacterial contamination was observed under the tested conditions.
These results are thus considered to provide a rational biophysical background for the use of caffeine in agar-jelly.

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