Weight-band-based simplification of oral allometric miltefosine dosing in paediatric patients with visceral leishmaniasis.

BACKGROUND AND

OBJECTIVES

An allometric miltefosine regimen dosed based on fat-free mass (FFM) is effective and safe in treating children with visceral leishmaniasis (VL). However, its complexity hinders successful implementation in endemic areas. We aimed to develop a simplified dosing based on weight bands (WBs) that achieves equivalent miltefosine exposure in a paediatric VL population using a simulation-based approach.

METHODS

Utilizing demographic data from 9379 Eastern African paediatric VL patients, WHO-CDC growth curves were adjusted to create a realistic virtual paediatric VL population. The virtual children were given either an allometric FFM-based, a WB-based or a 2.5 mg/kg dosing of miltefosine per day. To compare the regimens, two pharmacokinetic metrics were derived from the simulated patient population receiving the allometric FFM-based regimen: the 5th percentile of the time above the concentration associated with 90% in vitro intracellular parasite killing for efficacy and the 95th percentile of the AUC for safety. The performance of the dosing regimens was evaluated for both 14- and 28-day regimens.

RESULTS

A virtual population was constructed that closely resembled real-world paediatric Eastern African VL patients' height- and weight-for-age distributions. Target attainment rates for the two pharmacokinetic metrics tested differed by less than 1.5% between the final WB- and FFM-based dosing regimens. The final doses in mg were 20 for children under 6 kg, 30 for 6.0-9.9 kg, 50 for 10.0-14.9 kg, 60 for 15.0-19.9 kg, 70 for 20.0-24.9 kg and 80 for 25.0-29.9 kg, for both 14- and 28-day regimens.

CONCLUSIONS

Our simplified WB-based dosing strategy offers a practical alternative for allometric miltefosine dosing in children, yielding satisfactory exposure levels.