ラットにおける蓚酸の生体内動態

Abstract

ラットを用いてradioisotopeで標識した蓚酸をトレーサーとして, 腎および肝クリアランス測定を行うとともに, pharmacokinetic studyを施行して解析し, イヌリンの場合と比較検討した.1)蓚酸の腎クリアランス値はイヌリンのそれの1.12倍であり, 蓚酸は糸球体で濾過されるとともに, 尿細管からも分泌されることが示唆された.2) Pharmacokinetic studyにより, 蓚酸は胆汁中にも排泄されるが, 腎摘群においては肝は腎の蓚酸排泄能を代償できなかったことから, 蓚酸の主要な排泄経路は腎であり, 生体内動態の亢進がそのまま腎での蓚酸排泄量増加に反映すると考えられた.3)蓚酸の生体内分布容積がイヌリンのそれの1.7倍であることは, 蓚酸は間質液中に容易に拡散し, また, 細胞内にも拡散していく可能性を示唆する

The pharmacokinetics of oxalate were studied in normal and nephrectomized rats, using radioisotope-labelled oxalate to resolve the mechanism of calcium oxalate stone formation. Plasma disappearance of 14C-oxalate was analyzed with a 2-compartment open model, and each compartment volume, the first-order rate constant for elimination, and the first-order rate constant for transfer between the central compartment and peripheral compartment were obtained. These values were compared with those for inulin. In normal rats, the total distribution volume was 57% of body weight for oxalate and 34% for inulin. The elimination rate constant from the central compartment for oxalate was lower than that for inulin, but oxalate had a much larger central compartment volume than inulin. Thus, the total clearance of oxalate was greater than that of inulin. In nephrectomized rats, total clearance of oxalate decreased to 1/6 of that in normal rats, while total clearance of inulin decreased to 1/27 of that in normal rats. These results suggest that oxalate is more diffusible than inulin, and that oxalate is excreted mainly from the kidney.