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

Abstract

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

“…Also, the AUC in the stratum corneum in the present study were clearly higher than those after p.o. administration in our previous reports . These findings indicate that WBBM can deliver IVM efficiently to the stratum corneum, and good therapeutic effect for scabies treatment is expected.…”

“…), the concentration of IVM in the stratum corneum was clearly higher than that after p.o. administration of IVM in our previous reports . This fact suggests that the 1–5 min bathing was enough to achieve the effective exposure level in the stratum corneum.…”

“…Then, the forearms and hands were wiped gently with a paper towel. Ten minutes later, the stratum corneum in the forearms was collected by the tape‐stripping method using D‐squame ® Skin Sampling Discs (CuDerm, Dallas, TX, USA) as described previously . The samples were stored at −20°C until measurement of the IVM concentration.…”

“…Ivermectin in the stratum corneum on the tape was extracted by acetonitrile and cleaned up by solid‐phase extraction as described in our previous reports . Each bathing fluid sample was diluted with three times its volume of acetonitrile.…”

Ivermectin to reduce malaria transmission I. Pharmacokinetic and pharmacodynamic considerations regarding efficacy and safety

“…This has led to several patients requiring treatment with parenteral veterinary formulations [17, 18]. Time since last meal does not seem to influence ivermectin's bioavailability, although this is still subject to debate [19, 20]. …”