Scabies is an intensely pruritic ectoparasitic skin infestation caused by the mite Sarcoptes scabiei and affects over 130 million people and hampers quality of life. 1 Topical permethrin, which is included in the World Health Organization's list of essential medicine, is the standard treatment for scabies. 2 In recent years, permethrin and ivermectin (IVM) have become the most relevant treatment options for scabies. 3 Using external treatments is very laborious and must be applied completely to the whole body; scabies may recur if some areas are unpainted. 4 Conversely, although an oral preparation of IVM is convenient for treatment, it can cause some systemic adverse drug reactions such as liver dysfunction. 5 To address the problems mentioned above, as a novel external application, we devised a whole-body bathing for exposure to IVM (IVM-WBB) in which patients would simply be bathed in a fluid containing IVM. Previously, we demonstrated that IVM is delivered into the skin but not into the blood via IVM-WBB in rats 6 and healthy volunteers. 7 In healthy volunteers, no adverse drug reactions were observed and the maximum IVM concentration in the stratum corneum after IVM-WBB was much higher than that after oral IVM administration. 8 In this clinical trial, we aimed to examine the efficacy and safety of IVM-WBB in elderly patients with scabies.
| ME THODS
| Trial design and schedule of IVM-WBBA multi-institutional trial for elderly patients with scabies was conducted in cooperation with five hospitals and three nursing care facilities. The ethics committee of Tokyo University of Science (no. 12002) and each participating facility approved the trial. All trial procedures were conducted according to the Declaration of Helsinki. Figure 1 illustrates the schedule of IVM-WBB treatment and sample collection.
Tolvaptan efficacy for heart failure has a large interindividual variation. This study aimed to evaluate the influence of CYP3A5 and ABCB1 genotypes on tolvaptan pharmacokinetics and their relationships with plasma markers of CYP3A activity and laboratory test values in heart failure patients. Fifty‐eight heart failure patients receiving oral tolvaptan for volume overload were enrolled. Blood samples for determination of pre‐dose plasma concentrations of tolvaptan and its metabolites were collected. CYP3A5 and ABCB1 genotypes, plasma 4β‐hydroxycholesterol/total cholesterol ratio (4β‐OHC/TC) and 25‐hydroxyvitamin D (25‐OHD), and serum laboratory test values were evaluated. The CYP3A5*3/*3 genotype was associated with a higher plasma concentration of tolvaptan but not with its metabolic ratios. The ABCB1 3435C > T, 2677G > T/A and 1236C > T polymorphisms affected neither tolvaptan pharmacokinetics nor its metabolism. Plasma 4β‐OHC/TC and 25‐OHD concentration were not correlated with plasma tolvaptan concentration. In a stratified analysis based on CYP3A5 genotype, plasma 4β‐OHC/TC had a negative correlation with plasma tolvaptan concentration in the patients with the CYP3A5*1 allele, while the plasma concentration of 25‐OHD did not. The CYP3A5*3/*3 genotype was associated with a higher serum sodium level in the patients with volume overload. The plasma concentration of 25‐OHD had a positive correlation with the serum total bilirubin level. In conclusion, CYP3A5*3 but not ABCB1 genotypes elevated tolvaptan plasma exposure in heart failure patients. CYP3A5‐deficient patients treated with tolvaptan had a higher serum sodium level. The CYP3A5 genotype altered the relationship between plasma tolvaptan and 4β‐OHC.
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