The daily dose of ribavirin is currently determined on the basis of patient body weights. However, this is not considered to be adequate theoretically, since total plasma clearance of ribavirin (CLtotal) is due to hepatic metabolism and renal excretion. Recently, we proposed that the dosage of ribavirin be determined on the basis of renal function and body weight as the result of analyzing clinical data for 19 Japanese chronic hepatitis C patients. Thereafter, data were obtained for additional chronic hepatitis C patients (31 males and 16 females) and we re-evaluated the feasibility of using renal function for the determination of ribavirin dosage in the present study. A steady-state trough plasma concentration (Cpss) was achieved for ribavirin approximately 4 weeks after the initiation of treatment. There was marked variation in Cpss values among patients, and high ribavirin concentrations (>3500ng/mL) caused red blood cell disorders, as evaluated from plasma hemoglobin levels. Calculated as daily dose/body weight/trough Cpss, CLtotal for ribavirin was well correlated with the creatinine clearance (CLcr) of patients, and it was also well correlated with body weight, age, serum creatinine (S-Cr) and alanine aminotransferase (ALT) levels. This would indicate that CLtotal for ribavirin normalized by body weight is dependent on the renal function of the patient. Also, a linear relationship was observed between the predicted Cpss, which was estimated from body weight, dose and CLcr, and the observed Cpss (Observed Cpss=1.02×Predicted Cpss+27.71, 10 patients, r=0.6585). In conclusion, the determination of ribavirin dosages on the basis of renal function and body weight, rather than body weight alone, could be a better method of obtaining the plasma levels of ribavirin desired for achieving effective and safe treatment.
With the aim of improving the in vivo pharmacokinetic profile after rectal administration of the standard rifampicin (RFP) suppository, a new type of suppository containing a solid dispersion of RFP was prepared and evaluated in vitro and in vivo in rats. The RFP solid dispersion was prepared by mixing RFP powder with polyethylene glycol (PEG) # 3000 or #6000 in a weight ratio of 1 : 3 to make an amorphous condition. Based on an in vitro release study on RFP, Witepsol H-32 was selected as the suppository base instead of Witepsol H-15 that is used for the standard suppository. Further, with the Witepsol H-32 suppository, the in vitro release profile of RFP for a solid dispersion in PEG #3000 (H-32/SD 30) was superior to that for a dispersion in PEG #6000 (H-32/SD 60). The area under the concentration vs. time curve (AUC) of RFP from the H-32/SD 30 suppository after rectal administration was 2.8-fold that from the standard suppository. Addition of the absorption enhancers sodium deoxycholate, sodium ursodeoxycholate and gall powder to the H-32/SD 30 suppository increased the AUC of RFP after rectal administration 1.2-fold, 1.5-fold and 1.6-fold, respectively. Moreover, the AUC for the H-32/SD 30 suppository including gall powder was 80% of the AUC in the case of orally administering the same dose of RFP to rats. The results of this study showed that our new type of RFP suppository containing an RFP solid dispersion was effective in improving RFP dissolution and bioavailability after rectal administration.
Population/Method : Thirteen hemodialysis patients, who had received more than 3 months of Kalimate (KAL), a powdered preparation of calcium polystyrene sulfonate (PS-Ca), were enrolled in this test. Subjects were administered the same dose of Argamate Jelly (ARG), a jelly form of calcium polystyrene sulfonate (PS-Ca), for 3 months. During the test period, serum potassium values were measured and subjects answered questionnaires regarding compliance. ARG significantly reduced the amount of water used for administration and the majority of subjects preferred it to KAL. Serum potassium levels were well controlled throughout the study for both KAL and ARG. In conclusion, ARG is a useful drug because it maintains proper serum control, and was preferred to KAL by hemodialysis patients.
In recent years, the Ministry of Health, Labour and Welfare (MHLW) has actively promoted the use of generic drugs (GD) in order to reduce patients' drug costs and make more effective use of medical resources. We conducted a questionnaire survey on the use of GD by non-national hospital pharmacists in the Kinki region's six prefectures. In the responses, 80.9 % of hospital pharmacists considered that patients were paying more than before for their medicines and most felt that reconsidering the drugs used for prescriptions was a good way of reducing patient costs. Pharmacists who thought that GD would reduce medical expenses accounted for 69.2%. Those who actively dispensed GD replied that they did so because this aided hospital cost management and helped reduce patients' medical expenses. As the conditions for the use of GD in hospitals, most pharmacists gave “reliable supply”, “adequate product information” and “same quality as the original drugs”. However, 82.8% of the hospitals surveyed had an adoption rate of under 10% for GD. A major conclusion drawn from the survey was that GD were not fully used in non-national hospitals. In contrast, they are dispensed much more often in national hospitals where they are used on the basis of the standard check-list distributed by the MHLW, which has been providing this checklist and other GD information through its web net system since April 2004. We consider that the MHLW' s GD information should be made much more widely available.
We evaluated whether doctors' prescribed injections properly or not by examining information obtained from a pharmacist's checklist of cautions in the dispensing of injections, and used the results to investigate the current situation of checking injection prescriptions based on prescriptions for the 2002 calendar year. Cases in which pharmacists contacted doctors to check on drugs and dosing schedules were investigated and their numbers tallied. For the total of 23, 441 prescriptionsconsidered, the change rate was 0.97%. When we tallied change rates according to modality, that for antineoplastic drugs was 4.51% in 554 prescriptions, that for, IVH was 1.48% in 3, 313 prescriptions, and that for other injections was 0.69% in22, 284prescriptions. In addition, in the first six months of 2002, the prescription change rate was 0.68% and it almost doubled to 1.26% in the remaining 6 months of the year. The present study enabled pharmacists to provide information on the adverse effects of injections to doctors and nurses when dispensing them and aidedrisk management in our hospital.
At Kobe Pharmaceutical University, one of the pre-training programs for hospital pharmacy internship is on clinical pharmacy practice. It consists of three sections-pharmaceutical technology, pharmaceutical dispensing including TDM and drug information surveys. The pharmaceutical technology section was the first to be introduced. The purpose of the present study was to evaluate the content of the pre-training in pharmaceutical technology, which includes the measurement and evaluation of micromeritic properties (flow and packing properties) of pharmaceutical excipients, various tablet-related tests in the Japanese Pharmacopoeia, preparation of model vitamin granules and pharmaceuticals in the hospital pharmacy, and TPN. At the end of the training, students evaluated it by means of a questionnaire. Almost of all of the junior students who took the training participated actively and showed great interest in the preparation of pharmaceuticals. Overall, the questionnaire results indicated that more than 90% of the students had understood the training in pharmaceutical technology very well and felt it to be a valuable part of pre-training for hospital pharmacy internship.
In order to improve patients' understanding of prescribed medicines, we introduced the principles of universal design into drug information, basing this on the concept of providing easily understandable, user-friendly information in a visually appealing manner. In this report, we describe the use of visual effects in the provision of drug information. This was done according to the following 3 guidelines : 1) providing visual aids such as pictograms and illustrations in addition to text, 2) displaying information throughout the prescription rather than splitting it up into that pertaining to individual medicines, and 3) stratifying information according to clinical importance. The types of information to which this was applied included 1) information on substances used for pleasure (tobacco, alcohol, etc.), foods and beverages that are known to interact with prescribed medicines, for which patients should exercise caution, 2) information on daily living and the storage of prescribed medicines, and 3) information on the adverse effects of prescribed medicines. In a questionnaire survey conducted to compare our new format for providing drug information with conventional methods, most respondents thought that the great use of visual information made it easier to understand the drug information in their prescriptions. They were all very satisfied with it, and most hoped that it would be continued. In conclusion, applying universal design to the drug information would help greatly in achieving safe and effective drug therapy meeting the diverse needs of our aging society.
We carried out a retrospective medical chart survey to clarify the effects of various patient factors on warfarin dose requirements. Age, body weight, biochemical data and daily warfarin dose were recorded for 332 outpatients stabilized on warfarin. We found that there was a negative correlation between age and therapeutic warfarin dose (r=-0.3089, p<0.01, n=332), and positive correlations between body weight and therapeutic warfarin dose (r=0.1623, p<0.05, n=213) and lactate dehydrogenase (LDH) concentration and therapeutic warfarin dose (r= 0.2071, p<0.01, n=328). The mean serum LDH levels in patients with and without valve prostheses were 561.82 ± 151.06 and 393.61 ± 113.66 IU/L, respectively (p<0.01), suggesting the release of LDH due to red cell hemolysis in patients with valve prostheses. Moreover, the correlation coefficient between LDH concentration and therapeutic warfarin dose in patients with valve prostheses was higher than that in patients without valve prostheses, such greater correlation between LDH concentration and warfarin dose also indicating warfarin-induced release of LDH from red blood cellsin patients with valve prostheses.