A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers

• Published in: Malaria Journal
• Main Authors: Oyoo George O, Kipkeu Chemtai, Jemutai Julie, Wenwa Ednah, Mwambingu Gabriel, Salim Amina, Anabwani Evelyn, Nyakundi Priscilla, Lodenyo Hudson, Bashraheil Mahfudh, Abdallah Ahmed M, Juma Rashid, Chilengi Roma, Muchohi Simon N, Kokwaro Gilbert, Niehues Tim, Lang Trudie, Nzila Alexis
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2011
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-10-63; https://doaj.org/article/1131aeb459b646baa78c36b051c6338f

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. Conclusion 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.