{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:22:28Z","timestamp":1790097748061,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T00:00:00Z","timestamp":1497484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Imatinib, a tyrosine kinase inhibitor, is the drug of choice for the treatment of chronic myeloid leukemia in Nigeria. Several studies have established interindividual and interpopulation variations in imatinib disposition although no pharmacokinetic study have been conducted in an African population since the introduction of the drug. This study explored a population pharmacokinetic approach to investigate the disposition of imatinib in Nigerians and examined the involvement of some covariates including genetic factors in the variability of the drug disposition with a view to optimize the use of the drug in this population. A total of 250 plasma concentrations from 126 chronic myeloid leukemia patients were quantified using a validated method. A population pharmacokinetic model was fitted to the data using NONMEM VII software, and the influences of 12 covariates were investigated. The mean population\u2010derived apparent steady\u2010state clearance, elimination half\u2010life, area under the concentration\u2010time curve over 24 hours, and volume of distribution were 17.2 \u00b1 1.8 L\/h., 12.05 \u00b1 2.1 hours, 23.26 \u00b1 0.6 \u03bcg\u00b7h\/mL, and 299 \u00b1 20.4 L, respectively. Whole blood count, ethnicity, CYP3A5*3, and ABCB1 C3435T were found to have significant influence on the apparent clearance, while the interindividual variability in clearance and interoccasion variability in bioavailability were 17.4% and 20.4%, respectively. There was a wide variability in apparent clearance and area under the curve compared to those reported in other populations. Thus, treatment with a standard dose of imatinib in this population may not produce the desired effect in most of the patients, whereas continuous exposure to a low drug concentration could lead to pharmacokinetic\u2010derived resistance. The authors suggest the need for therapeutic drug monitoring\u2013guided dose individualization in this population.<\/jats:p>","DOI":"10.1002\/jcph.953","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T21:43:53Z","timestamp":1497563033000},"page":"1554-1563","source":"Crossref","is-referenced-by-count":19,"title":["Population Pharmacokinetics of Imatinib in Nigerians With Chronic Myeloid Leukemia: Clinical Implications for Dosing and Resistance"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6722-1970","authenticated-orcid":false,"given":"Babatunde Ayodeji","family":"Adeagbo","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Obafemi Awolowo University  Ile\u2010Ife Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiwalade Adewale","family":"Olugbade","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Obafemi Awolowo 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