Cerebral uptake of mefloquine enantiomers in fatal cerebral malaria.

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.