title: Investigation of reproductive toxicity of piperaquine in mice.
abstract: Reproductive toxicity data for the antimalarial drug piperaquine (PQ) were obtained in pregnant mice (F(0)) and their offspring (F(1) and F(2)). PQ phosphate (0-300 mg/kg/day) was given to pregnant Swiss mice from gestational days 14-18. Two F(1) pups from each litter (one male and one female) proceeded to maturity and were mated within dose groups. Biochemical and haematological indices were determined, and liver and kidney histopathology was assessed in F(1) and F(2) mice at 4 weeks. There were no significant dose-related adverse effects, but leucocytes were mildly elevated (F(1) and F(2) mice) and serum albumin was reduced (F(1) only) in the 300 mg/kg/day group. Low plasma PQ concentrations were detected in F(1) mice at 4 and 8 weeks. Although we found no significant PQ toxicity, clinical data are lacking and monitoring of women and their infants for biochemical and haematological adverse effects is recommended when PQ is used in pregnancy.
authors.affiliation: School of Pharmacy, Curtin University of Technology, Bentley, Western Australia, Australia. Kevin.Batty@curtin.edu.au
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Batty
authors.forename: Brioni R
authors.initials: BR
authors.lastname: Moore
authors.forename: Verity
authors.initials: V
authors.lastname: Stirling
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Ilett
authors.forename: Madhu
authors.initials: M
authors.lastname: Page-Sharp
authors.forename: Keith B
authors.initials: KB
authors.lastname: Shilkin
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.forename: Harin A
authors.initials: HA
authors.lastname: Karunajeewa
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D000962:Antimalarials / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology; D019963:Clinical Chemistry Tests; D005260:Female; D006321:Heart / Q000187:drug effects; D006403:Hematologic Tests; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects*; D012709:Serum Albumin; D018675:Toxicity Tests; D010879:Piperazines
chemical_list: D000962:Antimalarials; D011804:Quinolines; D012709:Serum Albumin; C034759:piperaquine; D010879:Piperazines