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.
Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (-) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in 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 displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (-)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted.
Treague Limited, Cambridge, United Kingdom. rtansley@treague.com
Robert
R
Tansley
Julie
J
Lotharius
Anthony
A
Priestley
Fiona
F
Bull
Stephan
S
Duparc
Jörg
J
Möhrle
D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry* / Q000493:pharmacokinetics; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry* / Q000493:pharmacokinetics; D009325:Nausea / Q000139:chemically induced; D012727:Sex Characteristics; D014839:Vomiting / Q000139:chemically induced
D000962:Antimalarials; D015767:Mefloquine