Masayo Komoda

Guideline for the diagnosis and treatment of scabies in Japan (second edition)

The guideline has been prepared by the Japanese Dermatological Association to ensure proper diagnosis and treatment of scabies, as oral therapy became available on August 2006 under health insurance and its clinical use was expected to increase. For making a proper diagnosis, the following three points should be taken into consideration: (i) clinical symptoms; (ii) detection of the mite (Sarcoptes scabiei); and (iii) epidemiological symptoms. The diagnosis is confirmed if the mites or eggs are identified by microscopy or dermoscopy and so forth. Topical sulfur preparations, with only limited usefulness, are the only available topical drugs approved by health insurance coverage for treating scabies. Currently, crotamiton, benzyl benzoate and γ‐benzene hexachloride are also used clinically. It is important to apply these to the whole‐body, including hands, fingers and genitals. The dose for ivermectin is a single administration p.o. of approximately 200 µg/kg bodyweight with water before a meal. Administration of a second dose is considered, if new specific lesions develop or the mites are detected. For treating crusted scabies, concomitant administration of oral ivermectin and the topical preparation is necessary. Some safe and useful topical drug preparations are needed to be approved by health insurance.

Experimental study of pharmacokinetics of external, whole-body bathing application of ivermectin.

As a novel method improving the safety of conventional oral ivermectin (IVM) for scabies treatment, we conceived an idea called the “whole‐body bathing method”. In this method, the patients would bathe themselves in a bathing fluid containing IVM at an effective concentration. To evaluate the feasibility of the method, we investigated the IVM concentration in the skin and plasma after bathing rats in a fluid containing 100 ng/mL of IVM. After the bathing, the concentration of IVM in the skin was more than 400 ng/g wet weight and was maintained until 8 h after the bathing. The concentration was clearly higher than that in patients taking IVM p.o. as previously reported; IVM was not detected in plasma in the present study. Thus, the method would be a preferable drug delivery system for the skin application of IVM compared with p.o. administration.

Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies

Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high‐fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol® tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration‐time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09–1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM.

Pharmacokinetics of ivermectin applied topically by whole‐body bathing method in healthy volunteers

As a novel administration method of ivermectin (IVM) for scabies treatment, we proposed a “whole‐body bathing method (WBBM)”. In this method, the patients would bathe themselves in a bathing fluid containing IVM at an effective concentration. Previously, we demonstrated that WBBM could deliver IVM to the skin but not to the plasma in rats. In the present study, to assess the clinical validity of the method an arm bathing examination (first trial) and a whole‐body bathing examination (second trial) were conducted in healthy volunteers. In both the first and second trials, after bathing in fluid containing IVM, the exposure in the stratum corneum was higher compared with that after taking IVM p.o. as reported previously. IVM was not detected in plasma at any sampling point after the whole‐body bathing in the second trial. Furthermore no serious adverse events were found. These results in both trials suggest that WBBM can deliver IVM to the human stratum corneum without systemic exposure or serious adverse effects in healthy volunteers, and at concentrations that would be adequate for scabies treatment.

Reduction of Medical Cost through Pharmaceutical Inquiries by Community Pharmacists and Relation with Iyaku Bungyo Rates: A Nationwide Survey on Prescription Inquiries.

This nationwide survey aimed to evaluate reduction of drug and medical costs due to prevention of serious adverse drug reactions through pharmaceutical inquires by community pharmacist, and investigate relation with iyaku bungyo (separation of dispensing from medical practice) rates. Using the national list of pharmacies, 10% of pharmacies were randomly selected by prefecture and asked to participate in an Internet-based survey. The survey period was 7 days, from July 21 to July 27, 2015. Of the 5575 pharmacies queried, 818 responded to the survey (response rate: 14.7%). The proportion of inquiries to total prescriptions was 2.6%. Among these, the proportion of prescriptions changed in response to inquiry was 74.9%. An estimated 103 million yen was saved by reducing drug costs, and 133 million yen was saved by reducing medical costs due to prevention of serious adverse drug reactions. Comparison of prescription change rates between pharmacies with high and low iyaku bungyo rates indicated that the proportion of prescriptions changed was significantly higher in pharmacies with high iyaku bungyo rates than in those with low iyaku bungyo rates (78.2% vs. 69.9%, p<0.01). The findings suggest that inquiries about prescriptions are useful in ensuring the safety of pharmacotherapy and reducing the cost of healthcare. They also suggest that iyaku bungyo promotes prescription changes through inquiries, leading to proper use of pharmaceutical products.