A comparative study on the antiseptic effects of external medicines for eyes, ears, and nose was conducted using clinically isolated methicillin-resistant staphylococcus aureus (MRSA) and staphylococcus aureus ATCC No.6538 (S. aureus), one of the index bacteria employed in antiseptic tests. The efficacies of these external medicines against MRSA and S. aureus mainly depend on the antiseptics compounded in them. The effects of medicines incorporating benzalkonium chloride (BAC) against MRSA were not significantly different from those against S. aureus; neither MRSA nor S. aureus grew much within 6 hours after inoculation. The results obtained 6 hours after the inoculation by the use of medicines with chlorobutanol (CB), those with than admixture of paraoxylbenzonates (AP) such as methylparaben (MP) and propylparaben (PP), those with a mixture of MP and CB, and those with a mixture of AP and CB were 58 to 71% for MRSA and 63 to 78% for S. aureus. The bacteria were completetely eliminated 7 days later. Their efficacies against MRSA, however, were slightly weaker than those against S. aureus. The minimum inhibitory concentration values of eye drops were measured; the values of BAC against MRSA were slightly higher than those of S. aureus. No significant defferences, however, were observed between the AP and CB values.

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Using clinical monitoring data of cyclosporin A (CyA) from renal transplant patients at different disease phases, we examined the relationships between their CyA pharmacokinetic profiles and physiological factors. The concentration of CyA in whole blood was measured by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters of CyA estimated using a zero order absorption one-compartment model at different phases of therapy showed great between-and within-individual variations. The zero order absorption rate constant (k⁰) and the area under the blood concentration-time curve (AUC_0-12) during acute tubular necrosis (ATN), and after an episode of nephrotoxicity or graft rejection decreased markedly, whereas the volumes of distribution (Vd) at those times increased. In a correlation study, positive intercorrelations existed between hematocrit (HCT), k⁰/ Vd (normalized by the Vd) and creatinine clearance (Cl_Cr), suggesting that the change in renal function affects the absorption process of CyA, and that HCT is likely to becone an indicator for predicting CyA disposition. In this study, we discuss the clinical necessity of CyA whole blood level monitoring in consideration of the changes in physiological factors due to renal dysfunction.

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Various types of scored tablets were designed and evaluated in terms of ease of divisibility and weight variation of the two halves following the division. Tablets were prepared with a standard one-face score (I), a standard one-face score with side scores (II), a uniform allaround score (III), a standard one-face score with deep side scores (IV), an all-around score with deep side scores (V) and a deep one-face (VI). From the comparison of tablets I & VI, it was found that when the depth of the score was 30% of the tablet thickness, the tablets were easily divided by hand into two equal halves with a small weight variation. However, tablet VI was found to have a disadvantage with regard to practical production: the durability of the punched heads was not satisfactory. For an all-around score, the optimal ratio of the depth of the score on the side to the length on the face was found to fall within the 8 to 20% range. Tablets III and V were found to be easily and precisely divided [weight variation (CV): 5%>]. Our study clarified that the design of the score greatly affects the ease of divisibility of scored tablets as well as the weight variation of the two halves following the division.

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We investigated the in situ jejunal absorption of [6]-gingerol to determine the extent of its intestinal absorption after administering the drug solution (2 mg in 0.9% NaCl solution containing 5% Tween 80) into the closed jejunal loop in rats. The plasma concentration of [6]-gingerol in the mesenteric venous blood was measured periodically up to 60 min, and the drug levels in mucosal and muscular tissues were also determined at the end of the absorption experiments. In addition, the remaining amount of [6]-gingerol in the loop was determined. Initially, the blood cell-plasma partition of [6]-gingerol was investigated following intravenous administration (3mg/ kg) in rats to calculate the drug levels in whole blood from the plasma levels measured in the absorption experiments. The blood cell-plasma concentration partition ratio (K) for [6]-gingerol after instantaneous equilibrium was achieved was estimated as 0.489. The cumulative percentage of [6]-gingerol absorbed into the mesenteric venous blood by 60 min was estimated to be 10.86±2.61% of the initial dose. The recovery of [6]-gingerol was calculated by dividing the sum of the cumulative amount of [6]-gingerol absorbed in the mesenteric blood, the amount of the drug taken up by the jejunal mucosa and muscle at 60 min, and the remaining amount of [6]-gingerol in the closed loop by the initial dose, and was estimated as 58.7±9.2%. The residual 40% of the initial dose was not recovered as [6]-gingerol. These findings suggest that [6]-gingerol is absorbed to a considerable extent from the rat jejunal lumen, and, furthermore, that [6]-gingerol may be metabolized and/or decomposed to a substantial extent in the rat jejunal lumen and/or tissue.

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The sensitivity to drugs, the pH in the medium of extract from intestinal content (MEIC) and the utilization of carbohydrates in the strain isolated from multi-drug-resistant Enterococcus preparations (RP) were compared with those in the strain isolated from conventional Enterococcus prepations (CP). The RP showed higher resistance to penicillin and macrolide antibiotics than the CP, but less resistance to quinolone antibiotics. In the MEIC, the CP decreased the pH more markedly than the RP. Regarding utilization of carbohydrates, both the RP and CP had the similar patterns to the catabolisms of Enterococcus faecium, but different catabolisms were observed between RP and CP.

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The bioavailability of morphine following rectal administration of a hollow-type suppository containing morphine hydrochloride (10mg) in different-added forms was evaluated in patients under general anesthesia during operation. The hollow-type suppositories were prepared using Witepsol H-15, a suppository containing 1% morphine solution (morphine solution, 10mg/ml) or 10% morphine powder diluted with lactose (morphine powder, 100mg) in its cavity. The plasma concentration of morphine and its metabolite, morphine-3-glucuronide (M-3-G), were determined.
The mean C_max and AUC of morphine following rectal administration of the hollow-type suppository containing morphine solution were higher than those obtained from the suppository containing morphine powder, whereas the mean Cmax and AUC of M-3-G were lower than those following administration of the suppository containing morphine powder. The mean AUC ratio. of M-3-G to morphine following administration of the morphine-powder containing suppository was three times larger than that of the suppository containing morphine solution. The hollow type suppository containing morphine solution or powder could thus be useful for the pain control of patients with cancer.
These findings suggest that the hollow-type suppository containing morphine powder or solution, which could be adjusted to specific individual dosages, constitutes a useful clinical application for the cancer patient from the viewpoint of enhancing the quality of life.

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A convenient clean chamber system termed the “Clean Stage, ” was evaluated from a new general information chapter on the classification of clean rooms and clean zones for aseptic processing. No colony-forming microorganision including fungi were found on the floor surface in the “Clean Stage.” Furthermore, no microbial level of the air was recognized in the “Clean Stage.” The present observation, revealed that the microbial levels of the floor and air in the “Clean Stage” correspond to class M-1 of the new chapter.

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Construction of a database system compiling the medical and drug information appearing in the manufacturer's bulletins was prompted by the increasing need for pharmacists working with medical professionals to understand adequately the current status and perspective of medical services.
This demand has been further supported by the fact that medical information obtained from the manufacturer's bulletins has been confirmed to be very useful because of the straightforward explanations offered and the detailed, current therapeutic data presented for particular fields. The application software used for the database system is “MEGABOX-VP” (REED REX Co., Ltd.), a relational database. This system is composed of the eight files of bibliography, journal, content, object, drug information, medical technology, disease and ethical drug. Each file can be combined with any other file by window. The search for particular information is performed by combining key words or code numbers of files.

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Contamination of tegafur, an cytotoxic antimalignant agent, in packaging materials of 28 different tegafur capsules available on the Japanese market had been reproted by one of the authors. The study revealed that the tegafur contamination was not been limited to the outer shell of the capsules but extended, in some of the brands, to the exterior of the press-through package (PTP). Suggestions were made one year previously to the manufacturers of the brands to take measures to prevent the contamination from occurring.
The purpose of the present study was to follow up and investigate whether any improvement was subsequently made on these brands. The existence of tegafur at the outer shell of tegafur capsules, PTP inner pockets, PTP, and aluminum pillow packs was qualitatively tested by HPLC analysis of most of the brands reported in the previous study. At the surface of most packaging materials, the existence of the active ingredient, tegafur, was demonstrated, and the contamination in some of the brands exceeded that found one year ago. In addition to the previously investigated brands, mixed granules of tegafur and uracil were studied, revealing contaimination of tegafur at the surface of stripped package films. It was suggested that some definitive means should be taken to minimize the contamination and to prevent any potential safety problem from arising by those who continuously handle cytotoxic products.

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Propylthiouracil (PTU), an antithyroid drug, has been widely used to treat hyperthyroidism. Since any dosage form other than tablet form is not commercially available for PTU, it is necessary to prepare the powder by pulverizing the tablet when dose adjustment is required. To clarify the efficacy of pulverizing the PTU tablet, we investigated the content uniformity, adhesiveness and long-term stability of PTU in three kinds of powders prepared with different excipients; EFC lactose, powdered lactose and potato starch.
The content uniformity of PTU was excellent in all powders. In addition, there was no adhesion of PTU to two kinds of wrapping papers. On the other hand, dividing and packaging tests performed by automatic machine showed a slight effect of the excipients on PTU adhesion to the machine, specifically the lost amount of PTU after dividing and packaging was approximately 6-10% of the initial amount in all powders.
PTU in these powders was almost completely stable by 90 days under the following storage conditions: R. H. 92% at 30°C, exposure to light at room temperature, and protection from light at 5°C. In addition, there was no apparent difference in the remaining percentage of PTU among these powders under each of the storage conditions. However, PTU remaining under R. H. 92% at 30°C tended to be lower than those under other storage conditions.
The present findings suggest that these PTU preparations made by pulverizing tablets are applicable to practical long-term therapy use.

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Cefpiramide (CPM) is a third-generation cephem antibiotic characterized by its higher protein binding percentage, higher therapeutic concentration and longer biological half-life. We studied drug interactions of human serum protein binding between CPM and phenytoin (PHT), valproic acid (VPA) and salicylic acid (SA) with higher protein binding percentages. When CPM and SA were added to serum concomitantly, the percentages of the unbound concentration (free percent) of both drugs increased significantly over that of CPM or SA alone. However, when CPM and PHT were added similarly and also when CPM and VPA added in the same way, the free percentages of both drugs did not change significantly. These results confirmed the necessity to pay close attention to the interaction of serum protein binding between CPM and SA because increases in the free percentages of both drugs may adversely influence the clinical effects and therapeutic safety.

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We have prepared a medication instruction card, we call Patient Dispensing Instructions (PDI) to provide patients with useful information on such medication factors as pharmacology, adverse effects, and precautions in use. Each group of drugs (classified by pharmacological activity) has its own PDI for chronic disease use. Our investigation into the utility of the cards caused in 92 hospitals located in Ishikawa Prefecture produced generally favorable results. The range of arguments made by the selected hospitals concerning the contents of the cards were analyzed in an effort to improve the instruction card method.

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α1-Acid glycoprotein (α1-AG) concomitant in human serum albumin products and human plasma protein fraction products has recently received considerable attention because of its immunosuppressive properties.α1-AG is a serum protein present in normal humans that is augmented in the acute phase of inflammatory diseases and malignant tumors. The present study aimed at determining the exact content of α1-AG in several commercial products of formulations of human serum albumin and human plasma protein fraction. Those products examined were revealed to be feature by α1-AG in measurable concentrations that varied among the different manufactures.

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The hydrophilic membrane of a final filter was dissolved by etoposide injection (Lastet) when administered to a child with acute lymphoblastic leukemia by the continuous dosing method applied through a final filter. The objective of this investigation was to evaluate the effecacy (appearance, bubble point pressure and durability) of five final filters using etoposide injection and adjuvants. The results suggest that polyethylene glycol and ethanol in etoposide injection dissolved the cellulose membrane of the final filter, whereas the teflon membrane of the syringe-operated filter unit was valuable.

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In studying the use of Chinese herbal decoctions, a survey was conducted on out-patients seen at two hospitals in the Hokuriku district. Patients were questioned concerning preparation of the decoction (decoction time and kind of vessel to be used), dosage, occurrence of side effects, and extent of their compliance. The results showed that directions given to patients are inadequate or not fully comprehended. If therapy using Chinese herbal decoctions is to be effective, this problem must be resolved.

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The two methods of high performance liquid chromatography (HPLC) and bioassay have been reproted for determining arbekacin sulfate (ABK) in serum. The former method is inappropriate for clinical use due to inconvenient sample preparation, and the latter is insufficient because of its long assay time or influence of concomitant antibiotics. Therefore, the “TDx dibekacin kit” (TDx-DBK) for determination of serum arbekacin was used and evaluated in an effort to develop a practical method.
The calibration curve obtained demonstrated a good correlation (r=0.9993): the regression equation was Y=0.75X+ 1.15 within the 0-10μg/ml range. The coefficient of variation of within-run precision for five concentrations of arbekacin in serum (0.5, 1.0, 2.5, 5.0, 10. 0μg/ml) was less than 5% and that of between-run precision for three concentrations (1.0, 5.0, 10.0 μg/ml) was lesst han 7%.
The serum ABK (24 samples) concentrations were determined using this method and compared with those determined by HPLC. Good agreement was noted between the results derived by this TDx-DBK method and those by HPLC, where the correlation coefficient was more than 0.957. These results indicate that this TDx-DBK method may be useful for serum drug-level monitoring of patients undergoing ABK therapy.

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