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

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dc.contributor.authorChilengi, Romaen_ZA
dc.contributor.authorJuma, Rashiden_ZA
dc.contributor.authorAbdallah, Ahmeden_ZA
dc.contributor.authorBashraheil, Mahfudhen_ZA
dc.contributor.authorLodenyo, Hudsonen_ZA
dc.contributor.authorNyakundi, Priscillaen_ZA
dc.contributor.authorAnabwani, Evelynen_ZA
dc.contributor.authorSalim, Aminaen_ZA
dc.contributor.authorMwambingu, Gabrielen_ZA
dc.contributor.authorWenwa, Ednahen_ZA
dc.contributor.authorJemutai, Julieen_ZA
dc.contributor.authorKipkeu, Chemtaien_ZA
dc.contributor.authorOyoo, Georgeen_ZA
dc.contributor.authorMuchohi, Simonen_ZA
dc.contributor.authorKokwaro, Gilberen_ZA
dc.date.accessioned2015-11-11T12:02:08Z
dc.date.available2015-11-11T12:02:08Z
dc.date.issued2011en_ZA
dc.description.abstractBACKGROUND: 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 (Cmax) was 160-200 nM and after 6 hours, the effective concentration (Ceff) was <150 nM. CONCLUSION: Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff 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.en_ZA
dc.identifier.apacitationChilengi, R., Juma, R., Abdallah, A., Bashraheil, M., Lodenyo, H., Nyakundi, P., ... Kokwaro, G. (2011). A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers. <i>Malaria Journal</i>, http://hdl.handle.net/11427/14891en_ZA
dc.identifier.chicagocitationChilengi, Roma, Rashid Juma, Ahmed Abdallah, Mahfudh Bashraheil, Hudson Lodenyo, Priscilla Nyakundi, Evelyn Anabwani, et al "A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers." <i>Malaria Journal</i> (2011) http://hdl.handle.net/11427/14891en_ZA
dc.identifier.citationChilengi, R., Juma, R., Abdallah, A. M., Bashraheil, M., Lodenyo, H., Nyakundi, P., ... & Nzila, A. (2011). A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers. Malar J, 10(63), 10-1186.en_ZA
dc.identifier.ris TY - Journal Article AU - Chilengi, Roma AU - Juma, Rashid AU - Abdallah, Ahmed AU - Bashraheil, Mahfudh AU - Lodenyo, Hudson AU - Nyakundi, Priscilla AU - Anabwani, Evelyn AU - Salim, Amina AU - Mwambingu, Gabriel AU - Wenwa, Ednah AU - Jemutai, Julie AU - Kipkeu, Chemtai AU - Oyoo, George AU - Muchohi, Simon AU - Kokwaro, Gilber AB - 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 (Cmax) was 160-200 nM and after 6 hours, the effective concentration (Ceff) was <150 nM. CONCLUSION: Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff 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. DA - 2011 DB - OpenUCT DO - 10.1186/1475-2875-10-63 DP - University of Cape Town J1 - Malaria Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers TI - A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers UR - http://hdl.handle.net/11427/14891 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14891
dc.identifier.urihttp://dx.doi.org/10.1186/1475-2875-10-63
dc.identifier.vancouvercitationChilengi R, Juma R, Abdallah A, Bashraheil M, Lodenyo H, Nyakundi P, et al. A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers. Malaria Journal. 2011; http://hdl.handle.net/11427/14891.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2011 Chilengi et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceMalaria Journalen_ZA
dc.source.urihttp://www.malariajournal.com/en_ZA
dc.subject.othermethotrexateen_ZA
dc.subject.othermalariaen_ZA
dc.subject.otherantineoplastic agentsen_ZA
dc.subject.othernauseaen_ZA
dc.subject.othergastrointestinal diseasesen_ZA
dc.titleA phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteersen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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