人血浆和尿液中不同品牌灰黄霉素的体外释放及生物利用度

The in vitro liberation and the bioavailability of different brands of griseofulvin in plasma and urine in man.

作者信息

Terhaag B, Le Petit G, Pachaly C, Feller K

出版信息

Int J Clin Pharmacol Ther Toxicol. 1985 Sep;23(9):475-9.

Abstract

The bioavailability of griseofulvin in three different brands, two microfine forms (Gricin = G, Likuden = L), and one ultramicrofine form (Gris-PEG = GP), was determined in plasma and urine in six healthy volunteers in a crossover study and compared with in vitro liberation data. GP shows a higher AUCo infinity (140 +/- 24 mumol . h . l-1) and Cmax (4.5 +/- 0.1 mumol . h-1) than the microsize brands of griseofulvin (AUCo infinity:58 +/- 7, and 45 +/- 6 mumol . h . l-1; Cmax:1.7 +/- 0.2, and 1.5 +/- 0.2 mumol . l-1; G and L, resp.), but the same tmax at the third hour. There results correspond with the in vitro liberation data. Contradictory results of the bioavailability are found by determining the amount of 6-Demethylgriseofulvin eliminated in urine. The elimination of this main metabolite after dosing with L is lower (0.18 +/- 0.02 mmol) than those of the other two brands, which do not differ (0.31 +/- 0.04; 0.32 +/- 0.02 mmol, G and GP, resp.). It is concluded that the determination of bioavailability only by means of the eliminated amount of a metabolite in urine may produce false results.

摘要

在一项交叉研究中，测定了6名健康志愿者服用三种不同品牌、两种微晶型（Gricin = G，Likuden = L）和一种超微晶型（Gris - PEG = GP）灰黄霉素后的血浆和尿液生物利用度，并与体外释放数据进行了比较。与微晶型灰黄霉素品牌相比，GP的AUCo infinity（140±24 μmol·h·l⁻¹）和Cmax（4.5±0.1 μmol·h⁻¹）更高（G和L的AUCo infinity分别为58±7和45±6 μmol·h·l⁻¹；Cmax分别为1.7±0.2和1.5±0.2 μmol·l⁻¹），但tmax均在第3小时。这些结果与体外释放数据相符。通过测定尿中消除的6 - 去甲基灰黄霉素量发现了生物利用度的矛盾结果。服用L后该主要代谢产物的消除量较低（0.18±0.02 mmol），低于其他两个品牌（G和GP分别为0.31±0.04；0.32±0.02 mmol），后两者无差异。结论是仅通过尿中代谢产物的消除量来测定生物利用度可能会产生错误结果。