The determination of aminopyrin elimination for control of the metabolic capacity of the liver in man

Abstract. The kinetics of plasma and breath elimination of aminopyrine after ¹⁴C-aminopyrine given orally were studied using an open one-compartment model and first order rates of elimination. The study comprises eight healthy volunteers and two groups with histologically verified chronic liver diseases (cirrhosis, n = 12, and chronic aggressive hepatitis, n = 12). Elimination rates from plasma and breath were significantly reduced in the group with cirrhosis, but only so in chronic aggressive hepatitis when they were expressed relative to each other.
Monomethylaminopyrine was eliminated more rapidly compared to aminopyrine, and the rate of formaldehyde formation was positively correlated to the excretion rate of CO₂ ( r = 0.53, P <0.002). No correlation was found with clinical or other laboratory data in the groups of liver diseases studied.
The test is a quantitative indicator of the drug metabolizing mixed function oxidases of the endoplasmatic reticulum of the liver, and may reflect the degree of damage to this system in chronic liver disease.     

姜酚对小鼠肝药酶活性的影响

目的:研究姜酚对小鼠肝脏细胞色素氧化酶P450(CYP450)含量及其亚型CYP2E1与CYP3A活性的影响。方法:小鼠口服给药姜酚(200,100,50 mg.kg-1.d-1),5 d后钙沉淀法制备肝微粒体,测定并考察姜酚对小鼠肝重、微粒体蛋白、CYP450及CYPb5含量的影响;氨基比林法和红霉素法测定肝微粒体CYP亚型CYP2E1与CYP3A的活性。结果:姜酚高、中、低剂量(200,100,50 mg.kg-1.d-1)对小鼠肝重、蛋白含量无影响,能显著降低CYP450的含量以及增加CYPb5的含量(P<0.01);3种剂量姜酚均可抑制CYP2E1的活性(P<0.05),且随着剂量增加抑制作用增强,高剂量姜酚可以抑制CYP3A的活性(P<0.05)。结论:姜酚对小鼠CYP450含量及亚型CYP2E1,CYP3A活性有抑制作用,抑制程度与剂量有关。     

Hepatic [14C]aminopyrine demethylation capacity after portocaval shunting

The [¹⁴C]aminopyrine breath test (ABT) was used before and after surgical portocaval shunting in 29 cirrhotic patients, 15 with arterialization of the portal vein and 14 without. These two subgroups were comparable with regard to age, prothrombin time, serum albumin, serum total bilirubin concentrations, Child classification, and preoperative ABT. After portocaval shunt, a striking reduction in ABT values was observed after 6 and 12 months (90.7±8.0%,P<0.05 and 77.3±7.5%,P<0.005, respectively). No further decrease was observed between 12 and 24 months. The microsomal function was reduced to a greater extent in patients with postnecrotic cirrhosis (55±4.8%,P<0.01) than in those with alcoholic cirrhosis (84.8±10.4%,P<0.05). Arterialization of the portal stump of the portal vein did not prevent the reduction in hepatocellular function. No significant change in prothrombin time, serum albumin, or bilirubin concentrations was observed during the follow-up period in any of the groups. Overall, preoperative ABT was significantly higher in those surviving one year (0.29±0.12% administered dose) than in those who died within this time period (0.12±0.01%,P<0.005). This observation suggests that portocaval anastomosis induces an early decrease in microsomal function that is not prevented by arterialization of the portal vein. It also suggests that ABT might be helpful in selecting patients for shunt surgery.     

小诺霉素与复方氨基比林注射液的配伍实验

本文观察了硫酸小诺霉素与复方氨基比林注射液的配伍稳定性，结果表明两药混合后，在１ｈ内肌注是可行的。     

奇异值分解和主成分回归测定克感敏片三组分

将奇异值分解和主成分回归相结合,首次用于药物的含量测定,采用紫外分光光度法同时测定克感敏片中的非那西丁、氨基比林和咖啡因的含量．其结果明显优于最小二乘法．     

The effects of prostaglandin E2 on pregnancy and embryonic development in mice.

The prostaglandins comprise an important and unique group of naturally occurring biological regulators. These substances are currently being widely used for the induction of labor and termination of pregnancy. The effects of prostaglandin E2 (PGE2) on pregnancy and embryonic development were investigated in Swiss-Webster mice. PGE2 induced a high incidence of abnormal offspring in mice when administered subcutaneously on either day 9, 12 or 15 of gestation. In addition, fetal growth was significantly affected following treatment with the prostaglandin on either the 12th or 15th day of gestation.     

Effect of famotidine on oxidative drug metabolism

Summary Famotidine, a new H₂-receptor antagonist was tested for drug interactions using ¹⁴C-aminopyrine and antipyrine. Elimination of these model drugs was studied before and during 8 days of famotidine dosing in 8 healthy volunteers. Famotidine 40 mg b.d. did not inhibit aminopyrine ¹⁴CO₂ half-life or antipyrine clearance although an unexpected mild enzyme inducing effect could not be excluded. It is unlikely that famotidine will inhibit hepatic drug metabolism during routine clinical use as the daily dose is expected to be 40 mg/day but interactions should be looked for if more prolonged or larger doses are used.     

复方氨基比林注射液组分的统计模拟分光光度法测定

统计模拟分光光度法用于制订复方氨基比林注射液3组分的含量测定。本研究用全面交叉组合实验设计,获得有限但足够的实验数据,用逐步回归法构造反映无限实体在不同UV-VIS波长下吸收度与组分含量经验关系的“最优”数学模型,用改良单纯形法寻优求出未知样品诸组分的含量,得到了圆满的结果。     

Reduced liver function is the trigger for renal sodium retention following portal vein ligation in the rat

Sodium retention along with peripheral vasodilation are features of prehepatic portal hypertension. In several models of experimental liver damage, sodium retention occurs only when hepatic function, measured by the aminopyrine breath test (ABT-k), falls below a critical threshold. The relationship between renal sodium handling, ABT-k and systemic and renal haemodynamics in partial portal vein ligated (PVL) rats was examined to test the hypothesis that peripheral vasodilation was responsible for initiating sodium retention. Haemodynamic measurements were conducted early after surgery in portal hypertensive rats with and without sodium retention and in sham-operated controls. Compared with control, both PVL groups of rats had elevated portal pressure and lower peripheral vascular resistance (P<0.05). Sodium retaining-PVL rats had both lower ABT-k (0.95 ± 0.05 vs 1.38 ± 0.06 times 10^-2/min; P<0.05) and higher sodium balance (1.38 ± 0.09 vs 0.43 ± 0.09 mmol/day; P< 0.05) than non-sodium retaining PVL rats. No differences in plasma renin activity or noradrenaline concentrations were observed. In a separate group of rats, hydralazine-induced peripheral vasodilation did not induce sodium retention. These results suggest that the presence of peripheral vasodilation alone is not sufficient to trigger a sodium-retaining status. A factor, probably liver function-dependent, acting directly on renal tubules may be necessary for changes in renal sodium handling in this model.     

Conditional pharmacology: Expression of anti-inflammatory activity may require pre-existent inflammatory mediators and/or hormones

Aspirin, aminopyrine, azapropazone, bufexamac (100 mg/kg), and even high doses of copper acetate (50 mg/kg p.o.) showed no acute anti-inflammatory activity in the standard assay based on the carrageenan-induced rat paw oedema in healthy, normal rats. Repeating the assays in animals with pre-established inflammation revealed that these drugs are effective anti-oedemic agents. The acceptability of these agents in clinical practice may therefore rest on the fact that certain inflammatory mediators can support and/or induce the expression of an anti-inflammatory activity of agents, that are ineffective in animals not affected by additional inflammations. If misoprostol (a prostaglandin-E₁ analogue) is given p.o. together with the above test-drugs to healthy rats, the anti-oedemic properties of these drugs are revealed, suggesting that prostanoids may potentiate some of the NSAIDs which do not inhibit prostanoid synthesisper se.