西咪替丁与法莫替丁：对大鼠体内茶碱药代动力学的影响。

Cimetidine versus famotidine: the effect on the pharmacokinetics of theophylline in rats.

作者信息

Mojaverian P, Rocci M L, Saccar C L, Vlasses P H, Ferguson R K

出版信息

Eur J Drug Metab Pharmacokinet. 1985 Apr-Jun;10(2):155-9. doi: 10.1007/BF03189710.

Abstract

The effects of cimetidine and a new, potent H2-antagonist, famotidine, on the single dose pharmacokinetics of theophylline were examined in rats. Male Sprague-Dawley rats (6 rats/group) received an i.v. dose of theophylline (6 mg/kg) alone and in conjunction with an i.v. dose of famotidine (10 mg/kg) or cimetidine (10 mg/kg). Venous blood samples were collected serially for seven hours after theophylline infusion and analyzed for theophylline concentration by HPLC. Concomitant famotidine administration did not alter any of the pharmacokinetic parameters of theophylline (AUC0- infinity; 38.1 +/- 8.7 vs. 38.8 +/- 6.3 micrograms.hr.ml-1), while cimetidine demonstrated a significant reduction in theophylline systemic clearance (0.11 +/- 0.02 vs. 0.16 +/- 0.02 L/hr/kg; p less than 0.001), a 40% prolongation of half-life (2.8 +/- 0.9 vs. 2.0 +/- 0.5 hr), with no change in the volume of distribution (0.39 +/- 0.1 vs. 0.41 +/- 0.13 L/kg). These results suggest that in contrast to cimetidine, famotidine, a non-imidazole H2-receptor antagonist, does not interfere with theophylline disposition in the rat.

摘要

在大鼠中研究了西咪替丁和一种新型强效H2拮抗剂法莫替丁对茶碱单剂量药代动力学的影响。雄性Sprague-Dawley大鼠（每组6只）分别静脉注射单独的茶碱（6mg/kg），以及与静脉注射法莫替丁（10mg/kg）或西咪替丁（10mg/kg）联合使用。在输注茶碱后连续7小时采集静脉血样，并通过高效液相色谱法分析茶碱浓度。同时给予法莫替丁并未改变茶碱的任何药代动力学参数（AUC0-∞；38.1±8.7 vs. 38.8±6.3μg·hr·ml-1），而西咪替丁使茶碱的全身清除率显著降低（0.11±0.02 vs. 0.16±0.02 L/hr/kg；p<0.001），半衰期延长40%（2.8±0.9 vs. 2.0±0.5小时），分布容积无变化（0.39±0.1 vs. 0.41±0.13 L/kg）。这些结果表明，与西咪替丁不同，非咪唑类H2受体拮抗剂法莫替丁不干扰大鼠体内茶碱的处置。