title: Population pharmacokinetics of quinine in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda.
abstract: OBJECTIVE
  Oral quinine is used for the treatment of uncomplicated malaria during pregnancy, but few pharmacokinetic data are available for this population. Previous studies have reported a substantial effect of malaria on the pharmacokinetics of quinine resulting from increased α-1-acid glycoprotein levels and decreased cytochrome P450 3A4 activity. The aim of this study was to investigate the pharmacokinetic properties of oral quinine in pregnant women with uncomplicated malaria in Uganda using a population approach.
  
  
  METHODS
  Data from 22 women in the second and third trimesters of pregnancy with uncomplicated Plasmodium falciparum malaria were analysed. Patients received quinine sulphate (10 mg of salt/kg) three times daily (0, 8 and 16 h) for 7 days. Plasma samples were collected daily and at frequent intervals after the first and last doses. A population pharmacokinetic model for quinine was developed accounting for different disposition, absorption, error and covariate models.
  
  
  RESULTS
  Parasitaemia, as a time-varying covariate affecting relative bioavailability, and body temperature on admission as a covariate on elimination clearance, explained the higher exposure to quinine during acute malaria compared with the convalescent phase. Neither the estimated gestational age nor the trimester influenced the pharmacokinetic properties of quinine significantly.
  
  
  CONCLUSIONS
  A population model was developed that adequately characterized quinine pharmacokinetics in pregnant Ugandan women with acute malaria. Quinine exposure was lower than previously reported in patients who were not pregnant. The measurement of free quinine concentration will be necessary to determine the therapeutic relevance of these observations.
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Frank
authors: F
authors: Kloprogge
authors: Université Paris Descartes, INSERM U663, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Vincent de Paul, Paris, France.
authors: Vincent
authors: V
authors: Jullien
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Epicentre, Paris, France Mbarara University of Science & Technology, Mbarara, Uganda.
authors: Patrice
authors: P
authors: Piola
authors: Epicentre, Paris, France Epicentre, Mbarara, Uganda Malaria Group, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Mehul
authors: M
authors: Dhorda
authors: Epicentre, Mbarara, Uganda.
authors: Sulaiman
authors: S
authors: Muwanga
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Shoklo Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
authors: François
authors: F
authors: Nosten
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Nicholas P J
authors: NP
authors: Day
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Nicholas J
authors: NJ
authors: White
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Epicentre, Paris, France.
authors: Philippe J
authors: PJ
authors: Guerin
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand joel@tropmedres.ac.
authors: Joel
authors: J
authors: Tarning
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D011803:Quinine / Q000097:blood* / Q000627:therapeutic use; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000962:Antimalarials; D011803:Quinine
keywords: NONMEM; P. falciparum; population models