An attempt at administering a transdermal formulation of bisoprolol in patients with acute cardiac symptoms.

BACKGROUND: Bisono® is the world's first transdermal formulation of a bisoprolol, which is approved for the treatment of hypertension in Japan. We aimed to investigate the usefulness of this formulation in patients who were admitted to our hospital with cardiac symptoms suggestive of acute coronary syndrome or an acute exacerbation of heart failure. METHODS: This study involved a retrospective survey of medical records from September 1, 2017 to April 30, 2018 obtained from the Cardiovascular Center of Kyoto Katsura Hospital. The clinical data of patients on admission who had received a transdermal formula of bisoprolol (Bisono® tape) were retrieved; their blood pressure and heart rate data were analyzed in relation to the doses of Bisono® tape administered. RESULTS: Sixty-three patients received the Bisono® tape. Their final diagnoses included acute myocardial infarction, an exacerbation of heart failure, and atrial fibrillation. While there was no significant correlation observed between the administered doses of the drug and reduction in blood pressure achieved within 24 h after admission, there was a significant (p < 0.05) correlation between the doses of Bisono®tnd reduction in the heart rate within 24 h after admission (ΔHR0-24 h). Only one patient who received 8 mg of Bisono® exhibited temporal bradycardia (heart rate < 50 bpm). CONCLUSION: The transdermal formulation of bisoprolol may be useful for the early introduction of ß-blockers in patients admitted with cardiac symptoms associated with myocardial ischemia or heart failure. However, caution should be exercised because of the possible risk of hypotension.

A retrospective analysis of patient-specific factors on voriconazole clearance.

BACKGROUND: Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. We investigated the relationships of voriconazole concentration with patient-specific variables and concomitant medication to identify clinical factors affecting voriconazole clearance. METHODS: A retrospective chart review of voriconazole trough concentration, laboratory data, and concomitant medication in patients was performed. The concentration/dose ratio (C/D-ratio) was assessed as a surrogate marker of total clearance by dividing voriconazole concentration by daily dose per kg of body weight. RESULTS: A total of 77 samples from 63 patients were obtained. In multiple linear regression analysis, increased C-reactive protein (CRP) level (p < 0.05) and decreased albumin (Alb) level (p < 0.05) were associated with significantly increased C/D-ratio of voriconazole, and coadministration with a glucocorticoid was associated with significantly (p < 0.05) decreased C/D-ratio of voriconazole (adjusted r (2) = 0.31). Regarding CRP and Alb, receiver operating characteristic curve analysis indicated that increased CRP level and decreased Alb level were significant predictors of toxic trough concentration of voriconazole. For CRP, area under the curve (AUC) and cutoff value were 0.71 (95 % confidence interval (CI), 0.57-0.86, p < 0.01) and 4.7 mg/dl, respectively. For Alb, AUC and cutoff value were 0.68 (95 % CI, 0.53-0.82, p < 0.05) and 2.7 g/dl, respectively. A significant difference was seen in voriconazole trough concentration between patients with hepatotoxicity and those without (5.69 µg/ml vs 3.0 µg/ml, p < 0.001). CONCLUSION: Coadministration of glucocorticoid and inflammation, reflected by elevated CRP level and hypoalbuminemia, are associated with voriconazole clearance. We propose that early measurement of voriconazole concentration before the plateau phase will lead to avoidance of a toxic voriconazole level in patients with elevated CRP level and hypoalbuminemia, although further studies are needed to confirm our findings.

Multicenter study for environmental and biological monitoring of occupational exposure to cyclophosphamide in Japan.

PURPOSE: A multicenter field survey of environmental contamination and exposure of healthcare professionals to anticancer drugs were performed. SETTING: Three university hospitals, one cancer specialty hospital and two corporate hospitals from across Japan. METHOD: The environmental contamination with cyclophosphamide (CP) was investigated. A wipe examination was performed at six sites apiece in two divisions. The urinary excretion of the CP over 24 h was determined. The subjects of the survey included physicians, pharmacists, and nurses, for a total of seven at each facility irrespective of job title. The wipe samples were collected at 12 sites within two divisions at each facility. For the exposure survey, the total urine volume was determined, and a portion of the urine sample was then collected from each participants at each facility. Urine was collected for 24 h. The samples were determined by using the GC-MS method. RESULTS: Wipe examination: contamination with CP was identified at 50% of the sites. The concentration was high (CP > 1.00 ng/cm(2)) in the general environment in two hospitals and in the safety cabinet in one hospital. In the survey for the exposure of staff to anticancer drugs, 276 samples were obtained from 41 healthcare professionals. CP was detected in 90 samples obtained from 23 subjects. The amount of exposure was greatly different among the facilities. The urinary excretion of CP per subject was between 2.7 and 462.8 ng/24 h. The range of urinary excretion for each hospital was between 4.6 and 211.2 ng/24 h.

Photoelectrochemical sensor with porphyrin-deposited electrodes for determination of nucleotides in water.

A 5,10,15,20-tetra(4-pyridyl)porphyrin (TPyP)-deposited ITO electrode as a sensor of nucleotides using photocurrent change was prepared. The TPyP-deposited ITO electrode could repeatedly detect nucleotides having concentrations of the microM order by a decrease in the photocurrent.

Bioavailability of a morphine suppository is increased after intracolostomal administration in colostoma-constructed rabbits.

This study was performed to assess the pharmacokinetics of morphine and its major metabolites after its rectal or colostomal administration in rectal-resected (ROP) or colostoma-constructed (SOP) rabbits, respectively. The pharmacokinetics of morphine, morphine-3-glucuronide (M3G), and M6G in normal rabbits appeared to be similar to those in human, judging from their plasma concentration-time profiles and the susceptibility of morphine to first-pass metabolism. In SOP, but not ROP, rabbits, the plasma concentrations of morphine, M3G and M6G were significantly increased compared with those in normal rabbits. The AUC of morphine and its metabolites, and the F value of the former in the SOP group were greater than those in the control group, while the elimination half-life (t(1/2)) values were comparable in the two groups. In addition, the disposition of morphine and its metabolites after intravenous (i.v.) administration to SOP rabbits was almost the same as that in normal rabbits, suggesting that an increase in the rate of absorption of morphine in SOP rabbits was not due to inflammation at the absorption site caused by operation, but probably due to its increased solubility in loose stools. Therefore, great attention should be paid when morphine suppositories are intracolostomally administered to colostoma-constructed patients.

Decreased bioavailability of carbamazepine suppository after its intrarectal and intracolostomal administration to rectal-resected or colostoma-constructed rabbits.

The pharmacokinetics of carbamazepine (CBZ), one of the useful analgesic adjunctive agents for palliative care, and its major active metabolite, CBZ-10,11-epoxide (CBZ-E), were investigated after the intrarectal and intracolostomal administration of CBZ to rabbits with rectal-resection or colostoma-construction. In rectal-resected rabbits, the bioavailability of CBZ and the plasma level of CBZ-E after rectal administration were significantly lower than those in normal rabbits, and furthermore these values after intracolostomal administration to colostoma-constructed rabbits tended to be lower than those in rectal-resected ones. This decreased bioavailability of CBZ was thought to be not due to an increased first-pass effect, but to the lower CBZ absorption ability in the upper rectum and colon, since absorption profile of CBZ was not affected by first-pass metabolism. When the dose was increased based upon the difference in the absolute bioavailability values in the rectal-resected and colostoma-constructed rabbits, the decreased plasma levels of CBZ were restored to the control levels incompletely, and the elimination of CBZ and CBZ-E was retarded. These findings suggest that owing to the similarity of their pharmacokinetics in rabbit and man, the increment of dosages of CBZ should be avoided, when CBZ suppositories are administered to rectal-resected or colostoma-constructed patients.