Imipramine induced complete reversal of chloroquine resistance in Plasmodium falciparum infections in Sudan

The effect of imipramine on reversal of chloroquine (CQ) resistance was examined in 40 Plasmodium falciparum patients in Sudan. Parasites were considered resistant if it was still present in peripheral blood on day 3 following treatment with a standard dose of CQ (25mg/Kg body weight), early treatment failure (ETF). Patients proven to be infected with CQ resistant parasites were then given imipramine HCl (100 mg, in two divided doses), on day 3 following chloroquine treatment, for 3 days. Imipramine reversed CQ resistance, within 3 days, in all patients (cure rate of 100%), with mild to moderate side effects. The plasma level of CQ three hours after the initial dose (10mg/Kg body weight), was higher in patients with sensitive parasites (0.649 ± 0.04 × 10^-6mol/L) than in those with resistant parasites (0.585 ± 0.043 × 10^-6mol/L). However, this situation was reversed following imipramine administration, the CQ plasma levels in patients with resistant parasites (0.645 ± 0.089 × 10 ^-6mol/L) becoming significantly higher (P < 0.05) than in patients with sensitive parasites (0.397 ± 0.032 × 10^-6mol/L). The CQ plasma levels remained higher among the group infected with resistant P. falciparum on day 7 compared to the chloroquine sensitive group. The treatment regimen used was well tolerated, and the plasma concentration of imipramine and desipramine in treated patients accorded with that reported for in vitro reversal of CQ resistance.