title: Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis.
abstract: In an open-label sequential cohort study, we compared gastrointestinal (GI) disturbances and plasma tafenoquine concentrations after administration of single-dose (400mg daily x 3 days; n=76 males, 11 females) and split-dose (200 mg twice daily x 3 days; n=73 males, 13 females) tafenoquine regimens in healthy Australian Defence Force volunteers for post-exposure malaria prophylaxis. The female and male volunteers had comparable demographic characteristics (age, weight, height) in the single- and split-dose treatment groups. GI disturbances were generally mild and self-limiting for both groups. The frequency of nausea and abdominal distress was over two-fold higher in females than in males for both treatment groups. Reporting of GI disturbances in the single-dose group differed significantly between males and females, but this gender difference was not seen for the split-dose group. In those volunteers who experienced GI disturbances, the mean plasma tafenoquine concentrations 12 h after the last dose of tafenoquine were approximately 1.3-fold higher in females than in males (means+/-SD: 737+/-118 ng/ml vs. 581+/-113 ng/ml). These preliminary findings suggest that further studies are required in a larger number of females to determine whether there is a need to reduce the dose of tafenoquine to minimise GI disturbances in females.
authors.affiliation: Australian Army Malaria Institute, Enoggera, Brisbane, Queensland 4051, Australia. mike.edstein@defence.gov.au
authors.forename: M D
authors.initials: MD
authors.lastname: Edstein
authors.forename: P E
authors.initials: PE
authors.lastname: Nasveld
authors.forename: D A
authors.initials: DA
authors.lastname: Kocisko
authors.forename: S J
authors.initials: SJ
authors.lastname: Kitchener
authors.forename: M L
authors.initials: ML
authors.lastname: Gatton
authors.forename: K H
authors.initials: KH
authors.lastname: Rieckmann
mesh_terms: D000328:Adult; D000634:Aminoquinolines / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D000962:Antimalarials / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005767:Gastrointestinal Diseases / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D016780:Malaria, Vivax / Q000517:prevention & control*; D008297:Male; D009325:Nausea / Q000097:blood / Q000139:chemically induced; D012727:Sex Characteristics
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; C055852:tafenoquine