Plasma quinine concentrations in falciparum malaria with acute renal failure

Abstract

Plasma quinine (Qn) monitoring was performed in 32 patients with severe falciparum malaria (10 with acute renal failure (ARF) and 22 with other severe manifestations) who were treated with the standard regimen of 10 mg/kg body weight Qn dihydrochloride, with a loading dose of 20 mg/kg body weight. Median plasma Qn concentrations prior to the first dose on each day were approximately 10-30% higher in ARF patients than in non-ARF patients during acute infection. Seven patients underwent haemodialysis; 2 died after 2 cycles. There were no significant-changes in plasma Qn concentrations in patients with ARF during haemodialysis. No Qn was detectable in haemodialysate fluids. This suggests that dosage adjustment of Qn during haemodialysis is unnecessary. Cardiotoxity of Qn must be of concern in malaria patients with ARF after 3 days of Qn therapy, and ECG monitoring during Qn infusion is recommended in all severe malaria patients with persistent ARF. If there is any arrhythmia, the infusion should be discontinued. However, in some hospitals where ECG facilities are not available, reduction in Qn dosage in persistent ARF patients should be considered after the third day of therapy. The appropriate dosage reduction should be further studied. Monitoring of total plasma Qn concentrations (which has been used routinely) is of no value for predicting the cardiotoxicity in ARF patients; monitoring of free Qn would be more appropriate. However, ECG seems to be the practical procedure to monitor cardiotoxicity of Qn. It may be possible to use the QTc interval to estimate the Qn concentration in severe malaria patients without ARF, but not in patients with persistent ARF.