Ivermectin: Difficulties in resolving pharmacokinetic and pharmacodynamic relationships in onchocerciasis

Abstract

Aim: To elucidate the non-drug related factors involved in the unique actions of ivermectin and the disassociation between plasma ivermectin concentrations, the commencement of microfilaricidal effects and adverse events. Methods: A willing and consenting patient group was matched for dermal microfilariae and plasma ivermectin concentrations in our laboratory. The patients (20 in number) were skin snipped; treated with ivermectin ( 150 μg/kg of body weight) and further skin snipped every 12h for 72h. Simultaneous blood sampling was performed' to establish ivermectin concentrations in plasma. Adverse events were recorded for three days after dosing, Results: Plasma ivermectin peaked at 4h (44.0±2.9 ng/ml) and latency to ivermectin effect was Tin. There was an initial increase (over 12h) in the skin load of microfilariae (mf)from 47.6±2.5 mf/mg skin to 52.2±2.4 mf/mg skin followed by a decline over the next 60h. After 72h, plasma ivermectin concentrations and skin microfilarial densities declined to <10ng/ml and <5mf/mg, respectively. Adverse events were mainly of the Mazzotti type. Conclusion: Although ivermectin in single oral doses has shown considerable promise in the treatment of onchocerciasis, further investigations of the complexities outlined above are advocated.

Keywords

• ivermectin
• pharmacokinetics
• pharmacodynamics
• onchocerciasis