Pharmacology of absorption and distribution: optimal use of antimalarial drugs in the treatment of severe falciparum malaria in Kenya

Since 1989; a project at the KEMRI CRC Unit at Kilifi has focused on the design of appropriate and praticable regimens for the treatment of severe falciparum malaria. Initially; there was no data describing the absorption; distribution and elimination of quinine in Kenyan children; who constitute the great majority of patients. Pharmacokinetic studies were conducted to define these variables; which formed the basis for the design of appropriate and praticable treatment regimens. Even with optimal clinical management; the majority is high in cases of severe malaria treated with quinine at Kilifi. Alternative drugs have been studied in a search for a therapeutic regimen which will further reduce mortality

Phenobarbitone in young children with severe falciparum malaria

The mortality of cerebral malaria (CM) in children remains 10-40; and seizures have been shown to effect outcome adversely. Phenobarbitone (PB) is cheap; widely available in Kenya and reduces the incidence in adults with CM (single IM dose; 3.5 mg kg-1. Its value in children with CM is unkown. We have studied the pharmacokinetics and effect of PB in children with CM as a dose-finding exercise prior to controlled trial. 14 children entered the treatment group and 39 entered the control group. Over the first 6 h; the motor component of the coma score improved in 29 of the treatment group and 26 of the controls; was unchanged in 36 and 51; worsened in 7 and 8; and was not available in 29 and 13 respectively. The time taken to localise pain was 21 + 19 h (x+SD) in the treatment group; and 22 + 14 h in the control. There was no difference between the groups in the incidence of seizure; number of seizures during admission; incidence of neurological sequelae or mortality. Peak PB concentrations exceeded 15 mgL-1 in only 27 of patients. Prophylactic PB (10 mg/kg) has neither apparent benefit nor risk in young children with CM.; probably because of the low blood concentrations achieved