Cerebral uptake of mefloquine enantiomers in fatal cerebral malaria

Abstract

Patients and methods: The brain disposition of the enantiomers of the antimalarial mefloquine was studied in two post-mortem human cerebral biopsies after oral administration of the racemic mixture.

Background: Mefloquine (MQ) is an effective antimalarial drug used both for prophylaxis and treatment of chloroquine resistant Plasmodium falciparum. MQ is generally well tolerated in treatment. Minor side-effects have been described. Potentially serious neuropsychiatric reactions occur. The mechanism underlying the neurotoxicity is unknown, although a dose relationship is evidently involved.

Results: Mefloquine enantiomer concentrations were determined using a chiral liquid chromatographic method. Mefloquine concentrations were higher in brain compared to plasma. Studied in one patient, white matter concentrations were higher compared to grey matter concentrations.

Conclusion: Based on the ratios brain concentration/plasma concentration, the brain penetration of the (+) enantiomer is much higher than that of the (-) enantiomer.