著者

鈴木 信也 村山 悠佳 杉山 恵理花 関山 正夫 佐藤 均

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.7, pp.829-842, 2009

被引用文献数

8 3

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We established dose estimation formulae for renal-excretion drugs using the glomerular filtration rate (GFR), tubular secretion clearance (Sc), and unbound fraction of drug in plasma (fp) as a renal function index of physiological development in neonates and infants not more than 2 years of age. A dose ratio of (D_C/D_A)=clearance ratio of (CL_C/CL_A)≅(fp_C·GFR_C)/(fp_A·GFR_A) for neonates and infants/adults was applied to drugs with fp·GFR>Sc, while D_C/D_A=CL_C/CL_A≅(β·BSA_C+fp_C·GFR_C)/(β·BSA_A+fp_A·GFR_A) was applied to drugs with Sc>fp·GFR using the coefficient of each drug (β) and body surface area (BSA). Validity of the estimation formulae was investigated in drugs with fp·GFR>Sc such as vancomycin (VCM), arbekacin (ABK), fosfomycin (FOM) and norfloxacin (NFLX), and in drugs with Sc>fp·GFR such as digoxin (DGX) and amoxicillin (AMPC). First, we compared the clearance ratio (CL_C/ CL_A) of VCM, ABK, and DGX estimated by our method with those calculated using the Japanese population clear- ance values and those estimated allometrically (BSA_C/BSA_A). Next, we compared the established doses of all drugs investigated with the doses for neonates and infants calculated from the conventional dose estimation methods for children and our estimation formulae, and evaluated our method. As a result, favorable consistency was observed in the CL ratio for all drugs, and the doses of VCM, FOM, NFLX and AMPC calculated from our estimation formulae approximated the established doses. In conclusion, the validity of the dose estimation method using pharmacokinetic factors related to physiological development (i.e., GFR, fp, Sc) for renal-excretion drugs in neonates and infants was demonstrated.<br>