A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

01 Dec 2010

Robert Tansley, Julie Lotharius, Anthony Priestley, Fiona Bull, Stephan Duparc and Jörg Möhrle

The American Journal of Tropical Medicine and Hygiene

DOI: 10.4269/ajtmh.2010.10-0228


Racemic mefloquine is a highly effective antimalarial whoseclinical utility has been compromised by its association withneuropsychiatric and gastrointestinal side effects. It is hypothesizedthat the cause of the side effects may reside in the (–)enantiomer. We sought to compare the safety, tolerability andpharmacokinetic profile of (+)-mefloquine with racemic mefloquinein a randomized, ascending-dose, double-blind, active and placebo-controlled,parallel cohort study in healthy male and female adult volunteers.Although differing in its manifestations, both study drugs displayeda substantially worse tolerability profile compared with placebo.The systemic clearance was slower for (–)-mefloquine than(+)-mefloquine. Thus, (+)-mefloquine has a different safetyand tolerability profile compared with racemic mefloquine butits global safety profile is not superior and replacement ofthe currently used antimalarial drug with (+)-mefloquine isnot warranted.

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