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[利多卡因在轻度ANIT诱导的胆汁淤积和半乳糖胺诱导的肝炎大鼠口服及静脉给药后的清除率(作者译)]

[Lidocain clearance after oral and intravenous application in rats with low grade ANIT-cholestasis and galactosamine-induced hepatitis (author's transl)].

作者信息

Fuchshofen M, Heusler H, Lutz B, Mora E, Richter E

出版信息

Z Gastroenterol. 1980 Aug;18(8):436-42.

PMID:7434856
Abstract

Each of 6 rats with a low grade of ANIT-cholestasis and a low grade of GalN-hepatitis received either 3 mg Lidocain i.v. or 24 mg Lidocain orally. The plasma concentrations of Lidocain were measured over a period of 3 1/2 hrs. The systemic clearance of Lidocain (Cli.v. = Di.v. divided by AUCi.v.) was significantly increased on ANIT-cholestasis (17 +/- 3) and GalN-hepatitis rats (13 +/- 2) (control rats: 7 +/- 1 ml/min x 100 g bw). Oral clearance of Lidocain (Clor = Dor divided by AUCor) was not significantly different in the three respective groups. In both groups with experimental liver disease the hepatic blood flow--calculated by comparing the systemic to the oral clearance--was significantly increased (22 +/- 4 and 19 +/- 3 vs 8 +/- 1 ml/min x 100 g bw). Due to this increase, the hepatic extraction ratio of Lidocain was significantly decreased (ANIT-cholestasis 0.73 +/- 0.07; GalN-hepatitis 0.74 +/- 0.05; controls 0.85 +/- 0.03). Because of an increase of systemic Lidocain clearance, no toxic plasma concentrations were observed.

摘要

6只患有轻度ANIT诱导的胆汁淤积和轻度GalN诱导的肝炎的大鼠,每只分别静脉注射3mg利多卡因或口服24mg利多卡因。在3个半小时的时间内测量利多卡因的血浆浓度。利多卡因的全身清除率(Cli.v. = Di.v. 除以AUCi.v.)在ANIT诱导的胆汁淤积大鼠(17 +/- 3)和GalN诱导的肝炎大鼠(13 +/- 2)中显著增加(对照大鼠:7 +/- 1 ml/min x 100g体重)。利多卡因的口服清除率(Clor = Dor除以AUCor)在三个相应组中没有显著差异。在两组实验性肝病大鼠中,通过比较全身清除率和口服清除率计算得出的肝血流量显著增加(分别为22 +/- 4和19 +/- 3,而对照大鼠为8 +/- 1 ml/min x 100g体重)。由于这种增加,利多卡因的肝提取率显著降低(ANIT诱导的胆汁淤积为0.73 +/- 0.07;GalN诱导的肝炎为0.74 +/- 0.05;对照组为0.85 +/- 0.03)。由于全身利多卡因清除率增加,未观察到有毒的血浆浓度。

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