title: Anti-relapse activity of mirincamycin in the Plasmodium cynomolgi sporozoite-infected Rhesus monkey model.
abstract: BACKGROUND
  Mirincamycin is a close analog of the drug clindamycin used to treat Plasmodium falciparum blood stages. The clinical need to treat Plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals.
  
  
  METHODS
  cis-mirinicamycin and trans-mirinicamycin were evaluated as prophylaxis against early liver stages of Plasmodium berghei in mice and as antirelapse hypnozoiticides against Plasmodium cynomolgi in the Rhesus monkey (Macaca mulatta).
  
  
  RESULTS
  Mirincamycin was very effective against early liver stages of P. berghei in mice: both cis and trans enantiomers were 90-100% causally prophylactic at 3.3 mg/kg/day for 3 days orally. Both cis and trans mirincamycin, however, failed to kill dormant liver stages (hypnozoites) in the P. cynomolgi infected Rhesus monkey, the only preclinical hypnozoite model. Mirincamycin enantiomers at 80 mg/kg/day for 7 days orally, a dose that generated exposures comparable to that seen clinically, did not prevent relapse in any of four monkeys.
  
  
  CONCLUSIONS
  Although efficacy against early liver stages of P. berghei was thought to correlate with anti-hypnozoite activity in primates, for mirincamycin, at least, there was no correlation. The negative P. cynomolgi hypnozoite data from Rhesus monkeys indicates that mirincamycin is unlikely to have potential as a clinical anti-relapse agent.
authors.forename: Susan
authors.initials: S
authors.lastname: Fracisco
authors.forename: Paktiya
authors.initials: P
authors.lastname: Teja-isavadharm
authors.forename: Montip
authors.initials: M
authors.lastname: Gettayacamin
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, USA. jbe9320457@aol.com.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Berman
authors.forename: Qigui
authors.initials: Q
authors.lastname: Li
authors.forename: Victor
authors.initials: V
authors.lastname: Melendez
authors.forename: David
authors.initials: D
authors.lastname: Saunders
authors.forename: Lisa
authors.initials: L
authors.lastname: Xie
authors.forename: Colin
authors.initials: C
authors.lastname: Ohrt
mesh_terms: D000818:Animals; D019072:Antibiotic Prophylaxis; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002981:Clindamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D008253:Macaca mulatta; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D008813:Mice, Inbred ICR; D018512:Parasitemia; D016789:Plasmodium cynomolgi; D010966:Plasmodium vivax; D012008:Recurrence
chemical_list: D000962:Antimalarials; D002981:Clindamycin; C000867:mirincamycin