Affiliations 

  • 1 Applied Health Research Group, Aston Pharmacy School, Aston University, Birmingham, B4 7ET, UK. Electronic address: r.k.s.badhan@aston.ac.uk
  • 2 Ministry of Health Malaysia, Block E1, E3, E6, E7 & E10, Parcel E, Federal Government Administration Centre, 62590, Putrajaya, Malaysia; Aston Pharmacy School, Aston University, Birmingham, B4 7ET, UK
  • 3 Aston Pharmacy School, Aston University, Birmingham, B4 7ET, UK
J Pharm Sci, 2018 08;107(8):2236-2250.
PMID: 29626533 DOI: 10.1016/j.xphs.2018.03.026

Abstract

Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance, attention has turned toward ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiology-based pharmacokinetic model in healthy adults (20-50 years), pediatric (3-5 years/15-25 kg) subjects, and a representative adult malaria population group (Thailand). Dosing optimization demonstrating a twice-daily dose for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and pediatric subjects. Furthermore, to address the occurrence of CYP450 induction that is often encountered with antiretroviral agents, simulated drug-drug interaction studies with efavirenz highlighted that a 1-mg/kg once-daily dose for 5 days would counteract the increased ivermectin hepatic clearance and enable a time above LC50 of 138.8 h in adults and 141.2 h in pediatric subjects. It was also demonstrated that dosage regimen design would require consideration of the age-weight geographical relationship of the subjects, with a dosage regimen for a representative Thailand population group requiring at least a single daily dose for 5 days to maintain ivermectin plasma concentrations and a time above LC50 similar to that in healthy adults.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.