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.
In Japan, pyrethroid-resistant head lice have been increasing; however, only 0.4% phenothrin, a pyrethroid drug, is available as an over the counter formulation. In recent years, Sumithrin â Lotion containing 5% phenothrin (PHT) was approved for scabies. In the USA, Sklice â Lotion containing 0.5% ivermectin (IVM) is used for the treatment of pyrethroid-resistant head lice. Therefore, to enhance the treatment of head lice in Japan, we conducted a clinical study to confirm the efficacy and safety of a combination regimen of PHT and IVM (PI regimen). Twelve cases were enrolled and PHT was applied to all patients on day 1. On day 8, five patients (41.7%) were lice free, and PHT was applied again. Notably, seven patients were not lice free and were switched to IVM. The rate of patients who were lice free on the PI regimen, which was the primary end-point, was 75.0% on day 15 and 91.7% on day 22. No adverse events were reported. A genetic analysis of the head lice collected at each visit revealed a kdr mutation in all patients. These results suggest that the PI regimen is safe and effective for the treatment of pyrethroid-resistant head lice in Japan.
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.
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.
疥癬はヒト皮膚角質層にヒゼンダニ(疥癬虫,, an oral scabicide, is often administered to patients as a simple suspension via a feeding tube. It has been reported that the effectiveness of ivermectin administration via a feeding tube is dependent on the devices or techniques employed. This route of administration reduces the dose of ivermectin by 10-50% compared to that associated with oral administration. Therefore, here we propose appropriate devices and techniques. In this report, we compared the recovery ratio when a simple suspension was administered via transnasal tubes of different diameters, different materials, flushing water volumes, slack and bed angle. No differences in recovery ratio were observed following the use of tubes constructed from polyvinyl chloride, ethylene vinyl acetate, polyurethane, and silicone. Furthermore, no significant differences in ivermectin recovery were observed as a result of using tubes with diameters of 8 French (Fr) and 12 Fr. However, we found tubes with diameters of 7 Fr were blocked during use. Furthermore, no noticeable differences in the recovery ratio were observed after flushing water volumes higher or lower than the internal volume of the transnasal tubes. Slack in the tubes had no influence on the recovery ratio. In contrast, a 9% increase in the recovery ratio of ivermectin was observed when the patient's bed was angled at 30° compared to that when the bed remained horizontal.In conclusion, to ensure higher recovery ratios of ivermectin with administration via transnasal tubes, it is recommended that tubes with diameters over 8 Fr be used, and that an angle greater than 30 °be applied to the patient's bed.
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