title: A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers.
abstract: BACKGROUND
  Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers.
  
  
  METHODS
  Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days.
  
  
  RESULTS
  The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product) were reported. The maximum concentration (C(max)) was 160-200 nM and after 6 hours, the effective concentration (C(eff)) was <150 nM.
  
  
  CONCLUSIONS
  Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable C(eff) of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.
authors.affiliation: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya.
authors.forename: Roma
authors.initials: R
authors.lastname: Chilengi
authors.forename: Rashid
authors.initials: R
authors.lastname: Juma
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abdallah
authors.forename: Mahfudh
authors.initials: M
authors.lastname: Bashraheil
authors.forename: Hudson
authors.initials: H
authors.lastname: Lodenyo
authors.forename: Priscilla
authors.initials: P
authors.lastname: Nyakundi
authors.forename: Evelyn
authors.initials: E
authors.lastname: Anabwani
authors.forename: Amina
authors.initials: A
authors.lastname: Salim
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mwambingu
authors.forename: Ednah
authors.initials: E
authors.lastname: Wenwa
authors.forename: Julie
authors.initials: J
authors.lastname: Jemutai
authors.forename: Chemtai
authors.initials: C
authors.lastname: Kipkeu
authors.forename: George O
authors.initials: GO
authors.lastname: Oyoo
authors.forename: Simon N
authors.initials: SN
authors.lastname: Muchohi
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kokwaro
authors.forename: Tim
authors.initials: T
authors.lastname: Niehues
authors.forename: Trudie
authors.initials: T
authors.lastname: Lang
authors.forename: Alexis
authors.initials: A
authors.lastname: Nzila
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001774:Blood Chemical Analysis; D064368:Healthy Volunteers; D006801:Humans; D007630:Kenya; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D000962:Antimalarials; D008727:Methotrexate