meta-analysis is ranked among the highest-quality study designs, objective assessment criteria specific to meta-analysis have not been reported. As meta-analysis is complex in structure, we developed the Quality Score, which assesses the quality and format of meta-analysis. In this study, we attempted to assess the structure and quality of meta-analysis articles on type 2 diabetes. meta-analysis 2 diabetes from PubMed and the Cochrane Library. We then assessed the structure (PRISMA statement) and quality (the Quality Score) of the articles found by assigning scores. We further extracted articles above a certain level, and analyzed and organized the data with statistically significant differences. The initial search for meta-analysis articles identified 217 articles from PubMed and 25 from the Cochrane Library. Eight of the 25 articles from the Cochrane Library were also found among the articles from PubMed. Of the resultant 234 articles retrieved by the search formula, 44 were studied. The assessment score (0 – 100) for the structure (PRISMA statement) of meta-analysis was 60.2 ± 22.0 ％ (Mean ± SD), while the Quality Score was 53.0 ± 18.9 ％ . This study showed that the assessment of the quality of meta-analysis articles is linked to the assessment of the structure of the articles. In order to produce the great effect expected from diabetes medications, healthcare professionals are required to go beyond medication management and offer a wide range of therapeutic management. To do this, management priority should be given to items with secured evidence.
Enemas of sodium polystyrene sulfonate (SPS) in 20% sorbitol (20% Sor) have regularly been administered by an irrigator for the treatment of hyperkalemia. However, intestinal necrosis, which may be caused by the high osmolality of Sor, has been reported in some patients who received enemas of SPS in Sor.We prepared several SPS suspensions using a 5% glucose solution containing methyl cellulose (MC), hydroxypropyl cellulose (HP) or Avicel RC 591 NF (AB) as a vehicle, and examined the physicochemical properties (dispersibility, osmotic pressure, viscosity and dropping time from irrigator) of each suspension. Among the suspensions tested, the 1% ABG suspension, which was prepared as follows; SPS was suspended in 5% glucose solution containing 1% AB by mixing at 5, 000 rpm for 3 min on a homo mixer, showed the best results. The 1% ABG suspension was isotonic with physiological fluid. A predominant dispersibility of SPS, a low viscosity and a short dropping time from the irrigator were all obtained using this-suspension. The suspension was quite stable for at least 90 days at room temperature.In uremic rats which were made by performing a bilateral nephrectomy, the occurrence of intestinal necrosis and the effect on the serum level of potassium were investigated after the rectal administration of SPS suspensions. No significant pathological changes were noted in rats receiving a 1% ABG suspension. In addition, the 1% ABG suspension caused a significant decrease in the serum level of potassium from the control level.These results suggest that the 1% ABG suspension for enemas of SPS can be useful in the treatment of hyperkalemia.
Database usage was evaluated regarding the retrieval of drug-induced adverse effect case reports. A search of case reports was performed using the on-line Medline (Ovid). Forty case reports were extracted from “Reactions” (adis INTERNATIONAL) used as secondary literature on adverse effects. From the original titles and abstracts, the name of the drugs and adverse effects were translated into Japanease and used to search data sets. After 6 pharmacists received a 30-minute explanation on how to use Medline since they had no previous experience in using Medline at the time of this study, the accessibility to the original case reports was examined and evaluated for their hitting rates. The hitting rates of the original data were 40-75%, and the data was divided into high-rate and low-rate groups. A major cause of a low hitting rate was that the “explode” function was not utilized to extend the terms of adverse effects. As a result, the “explode” function was found to be an important factor in effectively using Medline, especially when terms are not adequately chosen to retrieve case reports on adverse effects.
Cimetidine (CIM), a histamine H2-receptor antagonist, has been demonstrated to reduce the clearance (CL) of a number of drugs. Up to date, 29 drugs, whose CLs are reduced by the coadministration of CIM, are listed under their package insert. We reviewed the original articles investigating the potential drug interaction between CIM and these drugs, and analyzed the relationship between the daily dosage of CIM and the alteration of the CL of the coadministered drugs.The decrease in the CL in the coadministration of CIM varied greatly from chlordiazepoxide with the largest decrease (56.7%) to mexiletine with the smallest (6.0%). The dose of the CIM described in original articles also varied greatly with the largest dose 2, 400 mg/day and the lowest 300 mg/day. A dose of over 800 mg/day of CIM, which is the upper limit of the usual dose in Japan, comprised 98% of all reported cases. A 1, 200 mg/day dose (16.6 mg/kg/day) of CIM, which was the most frequent dose described in the literature, was 2.5 times higher than the 400 mg/day dose (6.7 mg/kg/day) which is the usual dose in recent years in our country.The CL and serum trough concentration of theophylline (TP) were measured before and after the oral coadministration with a dosage of 400 mg/day or 800 mg/day of CIM for 5 days in four healthy subjects. The alteration in the serum trough concentration (about a 35% increase) and the CL (about 20% decrease) of TP induced by the coadministration of 800 mg/day of CIM, was much greater than that observed after the coadministration at 400 mg/day.These results suggest that the uniform change in prescriptions only based on the names of the drugs used in combination must be reexamined, and that it is necessary to improve the drug interaction-check system based on scientific evidence. after carefully evaluating the dose of the drug used.
THEODUR® Tablets 100 (TDR·T) and THEODUR® Dry Symp 20%(TDR·DS) are sustained-releasepme pamations of theophylline. The dissolution test was used to examine the effects of TDR·T and TDR·DS soaked with milk on the release of theophylline from these preparations. The dissolution of theophylline from TDR·T soaked with milk was slower than that of the control thus indicating a delay in the release of theophylline. Milk did not affect the dissolution of theophylline from TDR·DS. In conclusion, the diffemence between the structures of TDR·T and TDR·DS seemed to produce dif5erences in the dissolution of theophylline soaked with milk. Accordingly, patients are recommended to take TDR·T with water apd not with milk.
Aminoglycoside antibiotics are used to manage hemo-dialysis patients after hemodialysis. Using this protocol, the serum concentration of aminoglycoside antibiotics in such patients is kept at a higher level for a long time which thus induces a toxic effect of aminoglycoside antibiotics.We administered tobramycin (TOB) 90 mg to 2 dialysis patients with infectious disease before each hemodialysis, then TOB was removed from the patients by hemodialysis after several hours.One patient was given TOB 90 mg 17 times over 33 days without any symptoms of either ototoxicity or dizziness. Another patient was given TOB 90 mg 5 times over 13 days, and his infectious condition improved markedly.The administration of aminoglycoside antibiotics before hemodialysis was thus suggested to be safe and effective for the treatment of infectious diseases in dialysis patients.We analyzed the postantibiotic effect (PAE) and the postantibiotic effect subMIC effect (PASME) of TOB for Pseudomonas aeruginosa ATCC 27853 in vitro. As a result, higher concentrations of TOB (4 MIC) and a longer exposure to it were thus found to induce stronger PAE and PASME.We therefore recommend that aminoglycoside antibiotics be given before hemodialysis in dialysis patient, and thereafter they should be removed, by hemodialysis after several hours, because high concentrations of arninoglycosides in the serum for several hours can induce stronger PAE and PASME enhance the efficacy and safety of aminoglycoside in addition to its own bacteriocidal activity.
At our hospital, we have been conducting experiments on the time course of bactericidal effectiveness of disinfectants against clinically isolated bacterial strains. In the present study, we investigated the following commonly used disinfectants; chlorhexidine gluconate (CHG), benzalkonium chloride (BAC), povidone iodine (PVP-I) and alkyl diaminoethylglycine hydrochloride (ADG). The results showed that PVP-I exhibited the greatest bactericidal effect among these disinfectants with a bactericidal time of within 20 seconds for both gram-positive and gramnegative bacteria. CHG, BAC and ADG appeared to have a relatively delayed bactericidal time against gram-positive bacteria and 7 of 9 strains tended to show resistance to these disinfectants. These findings point to the need to add ethanol in order to ensure the effectiveness of disinfec tion when using these agents. Furthermore, these disinfectants showed only poor bactericidal effectiveness at low concentrations against gram-negative bacteria, thus indicating that caution is needed when determining the appropriate concentration levels. Moreover, since our results for BAC and PVP-I differ from those described in our previous reports, extreme care is thus called for when determining the concentration levels and exposure times due to intrinsic bacterial factors and the time course of bactericidal effectiveness.
Cilostazol is being developed for the treatment of intermittent claudication due to peripheral arterial disease (PAD). In this study, we measured the serum cilostazol concentrations and platelet aggregations induced by adenosine diphosphate (ADP) and collagen, and also investigated the pharmacokinetics and pharmacodynamics of cilostazol in inpatients receiving cilostazol therapy. No significant difference was observed in C/D (serum trough concentration/dose) between males and females. A trend toward increasing the serum cilostazol concentration by increasing the dose (mg/kg) was observed (P<0.05). The interindividual variation of the C/D for cilostazol was found to be very large. No significant difference was observed between the C/D for cilostazol and the age, GPT or Ccr. A statistical correlation was observed between the serum cilostazol concentration and the maximum extent of aggregation (%) induced by ADP and collagen (P<0.05).
The pharmacological spectrum of triazolam (TZ), estazolam (ES) and zopiclone (ZP) in mice given benzodiazepine receptor agonists (BZ-RAs) by i.p. injection were investigated. The altertness, grooming, grip strength and locomotor activity assessed by Irwin's method were suppressed at 30 min after the injection of these drugs. In contrast, the injection of these drugs induced a head-twitch response, which is regarded as an experimental model for hallucination. These behavioral changes induced by TZ, ES and ZP with respect to the monoaminergic effect on behavioral pharmacology are also discussed.
Various pharmaceutical preparations are prepared in hospital pharmacies on a daily basis. The Product Liability (PL) Law has been in effect since July 1995 in Japan. To clarity the influence of the PL Law on the pharmacy service for hospital preparations, the frequency of preparation requests, preparation quantities, and the total preparation time of each hospital preparation were investigated retrospectively for 5 fiscal years (April to next March) from April 1993 to March 1998 at Yamaguchi University Hospital. Hospital preparations were classified into three categories based on the raw materials used. The category I preparations were prepared from the medicines listed in the National Health Insurance price standard for medicine, and were used according to the Pharmaceutical Affairs Law. The category 2 preparations were prepared from the medicine listed on the standard price lists and were used outside the jurisdiction of the Pharmaceutical Affairs Law. The category 3 preparations were prepared from chemical agents not listed in the standard price lists. It is necessary to get the approval of the Institutional Review Board at our hospital before category 2 and 3 preparations can be used. The request frequency and preparation quantity of category 1 preparations gradually decreased during the investigation period, while category 2 preparations remained almost constant. On the other hand, those of category 3 preparations steadily increased from 1993 to 1997. In addition, the total preparation time of the hospital preparations gradually increased year by year, and the preparation times for 1997 reached 110 percent of that for 1993. These results indicate that the pharmacists in our hospital have adequately understood the importance of the hospital preparations and have been adhering to the special preparation orders from each physician. As a result, it appears that the PL Law has not substantially affected the pharmacy service for pharmaceutical preparations in our hospital.
The effect of the dosage of methotrexate (MTX) on pharmacokinetic parameters in renal, hepatic and hematological functions were investigated. Twenty osteosarcoma patients (age: 13-53 years) received MTX infusions (dosage: 3.3-11.2g/m2) for 6 hrs. The serum MTX concentrations at 6h, 12h and 24h increased almost proportionally with the infused dose. The total serum MTX clearance and half-lives were almost constant in all the dosing ranges examined.To evaluate the relationship between the dosage and laboratory values, the patients were divided into three groups based on the MTX dosage and consisting of: low-dose (dosage: 3.3-5.2g/m2), middle-dose (dosage: 5.4-8.3g/m2), and high-dose (dosage: 9.0-11.2g/m2) groups. There was no significant difference between the renal and hematological functions before MTX infusion. In the high-dose group, significantly increased GOT and GPT values were observed on days 2 and 7, which indicate a decreased in hepatic function.In spite of the linear pharmacokinetics of MIX, a high-dose may cause remarkably nonlinear increased GOT and GPT values compared to those with low-and middle-doses.To avoid a severe adverse reaction of MTX therapy in the high-dosage group, careful monitoring of both the serum concentration of MTX and the liver functions is considered to be important after infusion.
In recent years, transdermal tape preparations have been widely used for numerous patients. A major problem related to the use of such tape is skin irritation. This adverse event is considered to be due to the impermeability of water through the tape material during adhesion and the occurrence of skin, eruption after its removal. As a result, the water permeability of the tape materials and the amounts of stratum comeum stripped from the skin were studied on five transdermal nitrate tape preparations. The water permeability of the preparation, in which the polyester membrane was used for the backing body, depends on the membrane thickness: a thinner membrane has a higher water permeability. The highest permeability was detected in the Antup® preparation. On the other hand, the amount of stratum comeum stripped from the skin was significantly lower when the new Frandol tape S® preparation was applied. According to these results and other drug information such as the cost of the preparation, we evaluated the quality of these products based on decision analysis criteria. This evaluation thus accurately indicated the effectiveness, safety and cost of the product. As a result, the highest score was obtained by the new Frandol tape S® preparation among the five tested products. This product showed the lowest amount of stratum comeum and the low incidence of side effects. In other words, new Frandol tape S® appears to be the most cost-beneficial transdermal nitrate tape preparation. The method used in this study was thus shown to be useful for the selection of the safest and most effective transdermal tape preparation.
The effects of an α-glucosidase inhibitor, acarbose on serum lipoproteins as well as hemoglobin A1c were studied in type 2 diabetes mellitus patients. Furthermore, the improving rates of hemoglobin A1c and serum lipoproteins were compared between the patients with and those without patient-counseling by a pharmacist.Acarbose was administered to 55 poor control type 2 diabetes mellitus patients for 4 months. Overall, the level of HbA1c was reduced by 1.55%. The reduction in patients with patient counseling (PC, n=17) was 2.1% while that in patients without such counseling (non-PC, n=38) was 1.05%(p<0.01). Total cholesterol and triglyceride levels were reduced in total by 7.7%, 21.8%, respectively, but the rate of decrease was significantly larger in PC than in non-PC patients (8.8% vs 5.3% for total cholesterol, 29.3% vs 10.1% for triglyceride, both p< 0.001). The Midband, which migrated between VLDL and LDL on polyacrylamide disc electrophoresis disappeared in 45% of the patients, and the Midband of PC disappeared in 60% of the patients, whereas the same rate for non-PC was 35%.These results suggested that the delayed glucose absorption by acarbose in type 2 diabetes mellitus improved the serum lipoproteins as well as the blood glucose level, and that patient counseling by a pharmacist significantly improved the efficacy of this agent.
A simple and fast determination of plasma panipenem (PAPM) in extremely low birth weight infants was established using reversed phase high-performance liquid chromatography. Solutions of 35% methanol (pH 5.8), including 5 mM NaH2PO4 and 5 mM sodium dodecylsulfate, were used for the mobile phase. The flow rate was 0.8 mL/min. UV detection was carried out at 300 nm. The pretreatment method was as follows: 200 mM 3-[morpholino] propansulfonic acid solution was added to the plasma as a stabilizer. It was then deproteinized with methanol. The calibration curve was linear in a range from 6.25μg/mL to 100μg/mL. The recovery rate from known concentration samples of PAPM was 98.4%. The within-run and day-to-day variations were below 2.5% and 2.7%, respectively. The PAPM concentrations in the plasma were determined in five infants. In immature patients, an extension of the half-life was also observed.
The serum drug concentrations in 6 cases of acute hydroxyzine intoxication patients were measured by HPLC. The patients were admitted about 1-10 hours after ingesting from 200 to 15000mg hydroxyzine. The serum hydroxyzine levels were within a range of 0.12-1.70μg/mL. The elimination half-lives were within a range of 4.7-111 hours during treating the patients by forced diuresis. The serum hydroxyzine levels associated with drowsiness was>0.51μg/mL, while that associated with vomiting was >0.51μg/mL and that with is miosis was> 1.40μg/mL. Only one fetal case was encountered. However, the fetal case could possibly have been due to trazodone rather than hydroxyzine because the concentration of hydroxyzine was 0.12μg/mL.
An investigation of package inserts was performed for 794 oral prescription drugs, in order to assess the package inserts as an information resource regarding the timing of drug intake which is important for rational usage of medicine. As a result, the number of package inserts which described the proper timing of drug intake was only 157 (20%). The timings of drug intake could be classified into five categories, i.e., before a meal, immediately before a meal, immediately after a meal, after a meal and between meals (at a hunger state). Evidence for the timing of drug intake is written in only 9% of the package inserts. However, such evidence could be provided from interview forms and original articles for 24% and 44% of the drugs, respectively. Furthermore, most of the evidence for the timing of drug intake (94%) was shown to be meant for either the appropriate onset of therapeutic actions (58%) or the prevention of adverse reactions (36%). On the other hand, there was a clear tendency that more evidence is provided for drugs which were put on market more recently. From these results, the information only from package inserts was found to be insufficient for the rational usage of medicine and that the timing of drug intake should thus be explained to patients based on additional investigation from interview forms and original articles as described in this study in order to achieve an improved efficacy and safety of drug administration.
( Received October 15, 1999 Accepted March 10, 2000 ) The hygroscopicity of the contents of clorazepate dipotassium (Mendon(R)) capsule (CM) divided in packages made of polyethylene laminated glassine was investigated by storing the capsules at various relative humidities (RHs). The CM capsules were found to significantly absorb water vapor at an RH of more than 61.5%. The hygroscopicity of CM decreased after placing the CM capsules into air-tight containers, e.g., polyethylene laminated glassine. At the same time, a marked discoloration of CM was also observed during storage, in which the color changed from white to yellow. The discoloration of the CM capsules accelerated at high RH levels and after expose to fluorescent light. As a result, when Mendon(R) capsules must be prepared in a powdered dosage form, CM should be stored below an RH of 31.3% and be protected from light to avoid any adsorption of water vapor and/or discoloration.
A tacrolimus injection is an immunosuppressant which is administered by an intravenous injection of drip infusion over a period from 4-24 hours. We herein investigated the factors effecting the loss of tacrolimus from the intravenous solution, and leaching di-2-ethylhexyl phtalate (DEHP, specified environmental estrogen) from the administration tube into the intravenous solution. The concentrations of tacrolimus and DEHP were measured by high-performance liquid chromatography (HPLC). The factors effecting the loss of tacrolimus from intravenous solutions were thus found to be the length and the inside diameter of the administration apparatus, the concentration of the tacrolimus solution and the drip rate of the solution. When the tacrolimus solution passed through an administration tube consisting of polyvinyl chloride (PVC) measuring 100 cm in length at a flow rate of 5.0 mL/h and an initial concentration 50μg/mL, the concentration of tacrolimus decreased to about 76% and 12μg/mL of DEHP leaked into the solution per hour. On the other hand, when using polyethylene or polyolefin tubes, the amount of tacrolimus did not decrease and no DEHP leaked into the solution. Therefore, when tacrolimus is administered in travenously in a solution from, PVC administation tubes should not be used.
A 56-year-old woman inpatient that had been administrated warfarin, digoxin, verapamil and disopyramide after undergoing surgery for a mitral and aortic valve replacement associated with artrial fibrillation received a 300mg daily dose of disopyramide therapy before and after the operation. Although the serum disopyramide concentration was within the normal therapeutic range, dry mouth appeared as a side effect. Disopyramide was thus changed to pirmenol. The trough level of pirmenol was 2.1μg/mL at seven days after starting pirmenol therapy at the dose of 300 mg/day, and the dose was there after decreased to 200mg/day. About two weeks after pirmenol therapy was started, liver injury was observed. At approximately 30 days after pirmenol administration was stopped, the liver function returned to a normal level.On the other hand, according to recent reports pirmenol was suggested to show a high level in the liver. The reported levels of pirmenol were also similar to for amiodarone and aprindine, which are both well known to induce side effect in the liver. Therefore, one of the reasons that pimenol induced liver injury may be due to its high levels in the liver.
The adsorption of marketed elcatonin (3 preparations) and salmon calcitonin (2 preparations) was examined. Each aqueous preparation in an ample was drawn into plastic syringes and then was stored still for 0, 1, 3, 5, 10, 30 or 60 min. The preparation was thereafter squeezed out of the syringe, and the remaining rate of elcatonin or salmon calcitonin in the solution was measured.In every elcatonin preparation, the remaining rate just after suction into the syringe was about 90%, and thereafter, the amount markedly decreased with time showing a rate of about 50% after 30 min. On the other hand, two salmon calcitoin preparations did not show any clear difference in these ratea. Namely, preparations containing gelatin as an ingredient showed a remaining rate of about 90% after up to 60 min of storage, and only a slight decrease was observed.In other preparations, the remaining rate at the point of suction into the syringe was about 90 %, but the rate thereafter decreased markedly to 50-60% affer 10 min.When administering elcatonin and salmon calcitonin preparations, sufficient attention should thus be paid to such adsorption in syringes.However, for elcatonin and salmon calcitonin preparations in syringes which do not require suctioning into the syringes, we found that the appropriate dose could be reliably administered.
