系数倍率法测定痛定注射液中三组份的含量

安痛定注射液中氨基比林、安替比林、巴比妥可采用系数倍率法和应用微机选择出合适的测定波长不经任何分离直接测出。氨基比林、安替比林和巴比妥的平均加收率分别为１００．２３％、９９．１３％和９８．４１％。     

Comparison of trimethadione and antipyrine as indicators of oxidative drug metabolizing capacity in man

Summary Ten healthy male volunteers were given trimethadione (TMO) 4 mg/kg and antipyrine (AP) 500 mg alone or concomitantly to determine whether the metabolism of the drugs was mediated by the same or closely related forms of cytochrome P-450.Whether administered alone or together the clearance (CL) and half-life (t_1/2) of TMO and AP were the same, and there was a good correlation between the CL and t_1/2 of TMO and AP (aloner=0.755 and 0.623, respectively; coadministeredr=0.771 and 0.503, respectively). Excretion of AP and its main metabolite and the clearance for production of AP metabolites after AP was administered alone were not significantly different when TMO and AP were taken together.When the two drugs were administered alone or coadministered, the correlation between the CL of TMO and the excretion of 3-hydroxymethyl-3-norantipyrine (NORA) was close (aloner=0.734, coadministeredr=0.749). The correlation between the CL of TMO and CLm of NORA when TMO and AP were given alone or concomitantly was 0.762 and 0.772, respectively.The findings suggest that TMO metabolism and the formation of NORA in healthy subjects are mediated by a closely related form(s) of the cytochrome P-450 system.     

Assay of antipyrine and its main metabolites 3-hydroxymethylantipyrine, norantipyrine and 4-hydroxyantipyrine in urine

Two assay methods for antipyrine (AP) and its main metabolites 3-hydroxymethylantipyrine (3-HMA), norantipyrine (NORA) and 4-hydroxyantipyrine (4-HA) in urine samples have been compared. Method I involved a 3 h incubation at 37°C with β-glucuronidase, whereas method II used acid hydrolysis with 3 M hydrochloric acid to convert NORA glucuronide to the aglycone and 24 h incubation at 37°C with β-glucuronidase for hydrolysis of 3-HMA and 4-HA glucuronides. The precision of both sample preparation procedures was evaluated by means of HPLC with UV detection. The relative standard deviation (RSD) for the metabolites were considerably greater than 10% with method I. Application of method II, however, led to intra-assay and inter-assay RSD of less than 10%.     

Pharmacokinetic parameters of antipyrine in dog after hepatectomy

Pharmacokinetic studies with antipyrine were carried out on beagle dogs to determine the consequence of hepatectomy on hepatic drug metabolizing capacity, the rate of hepatic regeneration, and the possible beneficial effect of hepatocellular transplantation. The drug (250 mg) was administered by short IV infusion in three groups of dogs (first group, 65% hepatectomy; second group, 65% hepatectomy with hepatocyte transplantation; third group 80% hepatectomy). Pharmacokinetic parameters of antipyrine were evaluated before surgery and within 10 d after surgery. Blood samples were taken at frequent intervals after drug administration and antipyrine was assayed in plasma by a specific HPLC method with UV detection. Before surgery, the mean elimination half-life was about 1.1 h and total clearance averaged 6 L h^?1. In dogs with 65% hepatectomy, no statistical differences in pharmacokinetic parameters of antipyrine appeared before or after surgery. When 65% hepatectomy was associated with hepatocyte transplantation, a significant increase in elimination half-life and a significant decrease in total clearance were observed. The same statistical differences in the pharmacokinetic parameters were observed in the group with 80% hepatectomy. Transplantation of isolated hepatocytes into the spleen did not correct hepatocellular insufficiency. In this study, numerous laboratory tests were performed. A significant correlation was found between serum albumin, cholesterol, factor V, ALAT, total bilirubin, and ratio of aminoacids and the pharmacokinetic parameters of antipyrine.     

安痛定注射液的多波长K系数法测定

本文采用多波长Ｋ系数法测定安痛定注射液的含量．氨基比林，安替比林和巴比妥的平均回收率分别是９８．９４％．１０１．１％，１０１．０％，相对标准偏差分别是０．４２％，０．４７％，０．５０％．结果表明，本法简便，实用．     

Antipyrine disposition and liver size in the elderly

Summary This study has examined the contribution of decrease in liver size to the decline in drug metabolising capacity which occurs with ageing. Liver volume and antipyrine kinetics were measured in two groups of healthy individuals aged 20 to 29 years and 75 to 86 years and in a group of hospitalised patients aged 70 to 89 years. Liver volume was reduced in both groups of elderly people compared to the young group. Antipyrine plasma half-life was prolonged and antipyrine clearance was reduced in the group of elderly normal individuals. In this group the index — antipyrine clearance per unit liver volume — was also reduced in comparison to that of the young group. Measurements of antipyrine elimination in the hospitalised elderly group did not differ significantly from those in the young group. It is concluded that both decreased liver mass and decreased hepatic enzyme activity contribute to the impairment of drug oxidation which occurs in the elderly and which may warrant a reduction in dosage of some drugs. However, differences have been demonstrated between groups of elderly people suggesting that under certain circumstances standard doses of such drugs may be normally tolerated.     

Phenazone (antipyrine) metabolism and distribution in young and elderly adults

1. The plasma half-life and apparent volume of distribution of phenazone (antipyrine) was studied in twenty-six normal adults (20–40 years of age) and twenty-six geriatric patients. 2. A wide range of values for plasma half-life was recorded in both groups (young 7·7–19·9 h, elderly 9·5–30·1 h) but the mean plasma half-life for the geriatric group (16·8 h; s.e.m. = 5·9) was significantly longer (P < 0·01) than the normal adult group (12·5 h; s.e.m. = 3·2). 3. No difference in plasma half-life was noted between sexes in either the geriatric or control groups. 4. Doubling the dose of phenazone from 10 to 20 mg/kg made no difference to the plasma half-life in a subgroup of the geriatric patients. 5. The volume of distribution of phenazone, representing total body water, was 0·59–0·63 l/kg in all groups except the elderly females, in whom it was 0·48 l/kg. This latter group showed a correspondingly higher plasma concentration extrapolated to time zero. 6. The difference in plasma half-life phenazone between normal adult and elderly groups is statistically significant, but the wide range of values in each group makes the biological significance less clear. Alteration of drug distribution with resultant higher plasma or tissue concentrations may contribute to adverse drug effects, particularly in the elderly female.     

Influence of phenobarbital on the disposition of clonazepam and antipyrine in the dog

Clonazepam (1 mg/kg) and antipyrine (0.1 mg/kg) were administered simultaneously by intravenous bolus injection to three dogs. After 2 weeks of chronic phenobarbital administration, the studies were repeated. Plasma concentration-time curves in all studies were biexponential. Phenobarbital administration increased total plasma clearances of clonazepam and antipyrine by 102% and 98.5%, respectively. Volumes of distribution were not altered, and consequently reductions in terminal exponential half-lives observed after phenobarbital were attributed to increases in clearances.     

Inhibition and induction of metronidazole and antipyrine metabolism

Summary The effect of cimetidine, antipyrine and phenobarbitone on the pharmacokinetics of intravenous metronidazole and oral antipyrine has been examined in 7 healthy volunteers. The administration of cimetidine for 24 h before and throughout the sampling period failed to alter the total clearance of metronidazole or the rate of formation of the hydroxy metabolite, whereas the total and partial clearances of antipyrine were decreased 0.74 and 0.6–0.7-fold, respectively, Seven days of phenobarbitone or antipyrine administration increased the total clearance of metronidazole 1.51- and 1.86-fold, respectively, and the total antipyrine clearance was 1.22 or 1.46-fold increased, respectively. The rate of metronidazole hydroxylation was significantly enhanced by both enzyme inducers. The partial clearance of antipyrine to the normetabolite was significantly increased by both inducers, wheras the rate of 4-hydroxylation was significantly increased only by prior antipyrine administration. The results indicate that the hydroxylation of metronidazole is not inhibited by cimetidine, but that it is inducible by phenobarbitone or antipyrine. It is suggested that metronidazole and antipyrine are metabolized by different enzymatic pathways.     

Measurement of hepatic drug-metabolizing enzyme activity in man

Summary Three parameters of hepatic drug metabolism, cytochrome P-450 (P-450) content, antipyrine metabolism and urinary excretion of glucaric acid (GA) were investigated in 161 patients who underwent diagnostic liver needle biopsy. P-450 and antipyrine metabolism, but not GA were related to histological changes in liver. All the parameters were significantly increased in subjects treated with enzyme-inducing drugs, the extent of induction being related to alterations in liver histology. The largest responses were seen in subjects with an intact liver and the smallest in those with hepatitis or cirrhosis. Therapy with inducers partly compensated for the impairement in drug metabolism caused by the disease process; thus, some patients with altered liver had normal values in the tests if they had been treated with inducers. There were significant correlations between in vivo and in vitro parameters of drug metabolism, but in the interpretation of data selection of the material and the parameters influenced the results. Thus, the antipyrine plasma clearance rate was directly related to P-450 and GA values, whereas the correlation between the latter and the drug half-life was non-linear. Also, comparison of selected groups of patients resulted in better correlations between the indices of drug metabolism than in the entire series. The results demonstrate that the overall picture of hepatic drug metabolism in man is largely determined by histological changes in the liver and by exposure to drugs, which are reflected differently in various assays of hepatic drug metabolism. Quantitative evaluation of these factors, and selection of the appropriate assay method, seem to be of importance in investigating hepatic drug metabolism in man.