Drug interaction between cyclosporine A and quinine in a renal transplant patient with malaria

We report a previously undocumented drug interaction between cyclosporine A and quinine. A 39 year old Asian with a recent renal transplant was diagnosed to have a mild cerebral falciparum malaria. He was treated with seven days of oral quinine (600 mg, 8 hourly), followed by a stat dose of pyrimethamine (75 mg)--sulfadoxime (1200mg) because of a strong suspicion of chloroquine resistant falciparum malaria. Using a polyclonal radioimmunoassay method, we measured morning trough cyclosporine A level before, during and after the quinine treatment. Results showed a gradual decrease in the cyclosporine A level from a baseline value of 328 ng/ml to 107 ng/ml after seven days of oral quinine with a subsequent rise to pre-treatment level after discontinuation of quinine. There was no significant change in the dose of cyclosporine A administered during the period of quinine treatment (4.05 to 3.83 mg/kg body weight). Biochemical liver function tests, serum creatinine and hematological parameters were also essentially unchanged during this period. In vitro study showed no significant methodological interference in the cyclosporine assay by quinine dihydrochloride. These findings suggest an in vivo drug interaction between cyclosporine A and quinine. The mechanism of this interaction is not clear. Further studies are required to confirm the significance of this observation. Quinine and its stereoisomer, quinidine should be used with caution until further information is available.