[Dose estimation for renal-excretion drugs in neonates and infants based on physiological development of renal function].
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 (DC/DA)=clearance ratio of (CLC/CLA) congruent with(fpC.GFRC)/(fpA.GFRA) for neonates and infants/adults was applied to drugs with fp.GFR>Sc, while DC/DA=CLC/CLA congruent with(beta.BSAC+fpC.GFRC)/(beta.BSAA+fpA.GFRA) was applied to drugs with Sc>fp.GFR using the coefficient of each drug (beta) 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 (CLC/ CLA) of VCM, ABK, and DGX estimated by our method with those calculated using the Japanese population clearance values and those estimated allometrically (BSAC/BSAA). 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.
Suzuki
Shinya
S
Faculty of Pharmaceutical Sciences, Showa University, Tokyo, Japan. shi-suzuki@umin.ac.jp
Murayama
Yuka
Y
Sugiyama
Erika
E
Sekiyama
Masao
M
Sato
Hitoshi
H
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate
D000900:Anti-Bacterial Agents