疟疾感染期间乙胺嘧啶的肝脏清除率降低。对离体灌注大鼠肝脏的研究。

Decreased hepatic elimination of pyrimethamine during malaria infection. Studies in the isolated perfused rat liver.

作者信息

Mihaly G W, Date N M, Veenendaal J R, Newman K T, Smallwood R A

出版信息

Biochem Pharmacol. 1987 Sep 1;36(17):2827-9. doi: 10.1016/0006-2952(87)90272-3.

Abstract

The elimination of the antimalarial drug pyrimethamine was studied in isolated liver preparations from young rats (80-100 g) infected with merozoites of Plasmodium berghei two weeks earlier. Perfusate half-life of pyrimethamine was increased in livers from M.I. rats (t1/2 beta control group = 56 +/- 11 min vs M.I. group = 101 +/- 12, P less than 0.01), reflecting a decrease in hepatic clearance (3.6 +/- 1.1 ml/min vs 1.9 +/- 0.5 ml/min, P less than 0.01). There was no significant difference in volume of distribution between livers from M.I. and control groups. Intrahepatic concentration of unchanged drug at 3 hr was 4-5-fold greater in livers from infected rats (control group = 4725 +/- 2287 ng/ml vs M.I. group = 22,324 +/- 6824 ng/ml), while liver: perfusate concentration ratios were not significantly different (control group = 30.8 +/- 24.1 vs M.I. group = 35.6 +/- 20.3). We conclude that the hepatic elimination of pyrimethamine is substantially impaired in the malaria-infected rat.

摘要

对两周前感染伯氏疟原虫裂殖子的幼鼠（80 - 100克）的离体肝脏制剂中抗疟药物乙胺嘧啶的消除情况进行了研究。乙胺嘧啶在感染疟疾大鼠肝脏中的灌注液半衰期延长（对照组t1/2β = 56 ± 11分钟，感染疟疾组 = 101 ± 12分钟，P < 0.01），这反映出肝脏清除率降低（3.6 ± 1.1毫升/分钟对1.9 ± 0.5毫升/分钟，P < 0.01）。感染疟疾组和对照组肝脏的分布容积无显著差异。感染大鼠肝脏中3小时时未变化药物的肝内浓度比对照组高4 - 5倍（对照组 = 4725 ± 2287纳克/毫升，感染疟疾组 = 22324 ± 6824纳克/毫升），而肝组织与灌注液浓度比无显著差异（对照组 = 30.8 ± 24.1，感染疟疾组 = 35.6 ± 20.3）。我们得出结论，在感染疟疾的大鼠中，乙胺嘧啶的肝脏消除功能严重受损。