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


Authors: Chilengi, Roma; Juma, Rashid; Abdallah, Ahmed M.; Bashraheil, Mahfudh; Lodenyo, Hudson; Nyakundi, Priscilla; Anabwani, Evelyn; Salim, Amina; Mwambingu, Gabriel; Wenwa, Ednah; Jemutai, Julie; Kipkeu, Chemtai; Oyoo, George O.; Muchohi, Simon N.; Kokwaro, Gilbert; Niehues, Tim; Lang, Trudie; Nzila, Alexis
Article 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.
Keywords: METHOTREXATE; MALARIA; ANTINEOPLASTIC agents; NAUSEA; GASTROINTESTINAL diseases
Journal Title: Malaria Journal
Volume: 10
Issue: 1
ISSN: 14752875
Publisher: BioMed Central  
Date Published: 2011-01
Start Page: 63
End Page: 71
DOI/URL:
Notes: --- - Article - ! '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 (CeffZ) was <150 nM. Conclusion: Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable CeffZ 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. [ABSTRACT FROM AUTHOR]' - Copyright of Malaria Journal is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) - ! 'Accession Number: 60415545; Chilengi, Roma 1 Juma, Rashid 2 Abdallah, Ahmed M. 1 Bashraheil, Mahfudh 1 Lodenyo, Hudson 2 Nyakundi, Priscilla 2 Anabwani, Evelyn 2 Salim, Amina 1 Mwambingu, Gabriel 1 Wenwa, Ednah 1 Jemutai, Julie 1 Kipkeu, Chemtai 1 Oyoo, George O. 3 Muchohi, Simon N. 1 Kokwaro, Gilbert 4 Niehues, Tim 5 Lang, Trudie 6 Nzila, Alexis 1,7; Email Address: alexisnzila@yahoo.co.uk; Affiliation: 1: Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya. 2: KEMRI-Centre for Clinical Research Nairobi, Kenya. 3: Department of Clinical Medicine and Therapeutics, University of Nairobi, Kenyatta National Hospital, P O Box 19701, 00202 KNH, Nairobi. 4: Consortium of National Health Research, Nairobi, Kenya, PO Box 29832-00202, KNH, Nairobi, Kenya. 5: Helios Klinikum Krefeld Academic Hospital, Lutherplatz 40, 47805 Krefeld, Germany. 6: Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, UK. 7: Departments of Chemistry and Clinical Pharmacology University of Cape Town Rondebosch 7701, Cape Town, South Africa.; Source Info: 2011, Vol. 10 Issue 1, p63; Subject Term: METHOTREXATE; Subject Term: MALARIA; Subject Term: ANTINEOPLASTIC agents; Subject Term: NAUSEA; Subject Term: GASTROINTESTINAL diseases; Number of Pages: 9p; Document Type: Article'
SU Authors
  1. Prof. Gilbert Kokwaro
    26 Kokwaro