2013 Fiscal Year Final Research Report
Clarifying about the variation factors of the pharmacokinetics of doxapram in low-birthweight infants.
| Project/Area Number |
23590189
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Daiichi University, College of Pharmaceutical Sciences (2013)
Kumamoto University (2011-2012) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
入江 徹美 熊本大学, 生命科学研究部, 教授 (60150546)
山﨑 俊夫 藤田保健衛生大学, 医学部, 教授 (40135364)
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| Project Period (FY) |
2011 – 2013
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| Keywords | ドキサプラム / 未熟児無呼吸発作 / 母集団薬物動態解析 |
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| Research Abstract |
This study aimed to determine the population pharmacokinetics of doxapram in low birth weight infants. A total of 92 serum concentration measurements obtained from 34 Japanese neonates were analyzed using nonlinear mixed-effect modeling (NONMEM). Estimates generated by NONMEM indicated that clearance of doxapram (CL; L/kg/h) was influenced by postmenstrual age (PMA; weeks), body weight (BW; g), and aspartate aminotransferase (AST; IU/L). In addition, the volume of distribution (Vd; L/kg) was influenced by gestational age (GA; weeks). The final pharmacokinetic model was: CL = BW/PMA x 0.0453 x serum AST -0.373; Vd = 2.54 (if GA >28 weeks) and Vd = 2.54 x 2.11 (if GA ≤ 28 weeks). The interindividual variabilities in CL and Vd were 39.9% and 83.0%, respectively, and the residual variability was 20.9%.
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