依诺沙星对大鼠体内茶碱肾清除率及代谢清除率的影响。
Effects of enoxacin on renal and metabolic clearance of theophylline in rats.
作者信息
Nadai M, Hasegawa T, Kuzuya T, Muraoka I, Takagi K, Yoshizumi H
机构信息
Department of Hospital Pharmacy, Nagoya University School of Medicine, Japan.
出版信息
Antimicrob Agents Chemother. 1990 Sep;34(9):1739-43. doi: 10.1128/AAC.34.9.1739.
The effects of enoxacin and its metabolite 4-oxoenoxacin on the disposition of theophylline were investigated in rats. Systemic clearance of theophylline was significantly decreased by approximately 40, 46, and 50% after oral coadministration of 25, 100, and 200 mg of enoxacin per kg, respectively. No significant changes in the volume of distribution of theophylline were observed. 4-Oxoenoxacin had no direct effect on theophylline disposition. Significant changes in urinary excretion of theophylline and its metabolites were observed. (i) Urinary excretion of unchanged theophylline was significantly increased in proportion to increases in enoxacin dosage. (ii) Decreases in renal clearance of theophylline and metabolic clearance of 1-methyluric acid and 1,3-dimethyluric acid were observed. (iii) The percent decreases in the metabolic clearance of 1-methyluric acid were dependent on enoxacin dosage. It is likely that enoxacin inhibits the elimination process, which depends on cytochrome P-450-mediated isozymes for N demethylation and oxidation, and that the capacity of the inhibitory effect of enoxacin is greater in the N-demethylation pathway than it is in oxidation.
在大鼠中研究了依诺沙星及其代谢产物4-氧代依诺沙星对茶碱处置的影响。分别口服每千克25、100和200毫克依诺沙星后，茶碱的全身清除率显著降低，分别约为40%、46%和50%。未观察到茶碱分布容积有显著变化。4-氧代依诺沙星对茶碱处置无直接影响。观察到茶碱及其代谢产物的尿排泄有显著变化。(i) 未变化的茶碱的尿排泄量随依诺沙星剂量的增加而显著增加。(ii) 观察到茶碱的肾清除率以及1-甲基尿酸和1,3-二甲基尿酸的代谢清除率降低。(iii) 1-甲基尿酸代谢清除率的降低百分比取决于依诺沙星剂量。依诺沙星可能抑制了依赖细胞色素P-450介导的同工酶进行N去甲基化和氧化的消除过程，并且依诺沙星在N-去甲基化途径中的抑制作用能力比在氧化途径中更大。
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