Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMINOPYRINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1995

Aminopyrine breath test improves long-term prognostic evaluation in patients with alcoholic cirrhosis in Child classes A and B.

In a 4-year survival study, we evaluated the prognostic value of the aminopyrine breath test and the Child-Turcotte-Pugh score in 190 alcoholic patients. Using aminopyrine breath test results, the patients were stratified into group 1 (aminopyrine breath test > 2%), group 2 (1% < or = aminopyrine breath test < 2%) and group 3 (aminopyrine breath test < 1%). Survival rates at 4 years were 68% in group 1, 35% in group 2 and 17% in group 3. Using the Child-Turcotte-Pugh score, survival rates at 4 years were 67% in Child-Turcotte-Pugh class A, 40% in class B and 7% in class C. To assess the value of aminopyrine breath test as an adjunct to Child-Turcotte-Pugh score in prognostic evaluation of patients with cirrhosis, two approaches have been used: a regression analysis using Cox's proportional hazard model by including the Child-Turcotte-Pugh score and aminopyrine breath test value, and the log-rank test to assess the prognostic value of aminopyrine breath test in each Child-Turcotte-Pugh class separately. The regression analysis showed that both parameters, the Child-Turcotte-Pugh score and the aminopyrine breath test results, were accepted in the model, suggesting that the aminopyrine breath test was still significantly related to survival once the Child-Turcotte-Pugh score had been entered into the model. Analysis of the prognostic value of the aminopyrine breath test in each Child-Turcotte-Pugh class separately indicated, however, that the contribution was negligible in the Child-Turcotte-Pugh class C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗
PubMed2001

Preliminary studies of a canine 13C-aminopyrine demethylation blood test.

The objectives of this study were to determine whether a 13C-aminopyrine demethylation blood test is technically feasible in clinically healthy dogs, whether oral administration of 13C-aminopyrine causes a detectable increase in percent dose/min (PCD) of 13C administered as 13C-aminopyrine and recovered in gas extracted from blood, and whether gas extraction efficiency has an impact on PCD. A dose of 2 mg/kg body weight of 13C-aminopyrine dissolved in deionized water was administered orally to 6 clinically healthy dogs. Blood samples were taken from each dog 0, 30, 60, and 120 min after administration of the 13C-aminopyrine. Carbon dioxide was extracted from blood samples by addition of acid and analyzed by fractional mass spectrometry. None of the 6 dogs showed any side effects after 13C-aminopyrine administration. All 6 dogs showed a measurable increase of the PCD in gas samples extracted from blood samples at 30 min, 60 min, and 120 min after 13C-aminopyrine administration. Coefficients of variation between the triplicate samples were statistically significantly higher for the %CO2, a measure of extraction efficiency, than for PCD values (P < 0.0001). The 13C-aminopyrine demethylation blood test described here is technically feasible. Oral administration of 13C-aminopyrine did not lead to gross side effects in the 6 dogs. Clinically healthy dogs show a measurable increase of PCD in gas extracted from blood samples after oral administration of 13C-aminopyrine. Efficiency of CO2 extraction from blood samples does not have an impact on PCD determined from these blood samples. This test may prove useful to evaluate hepatic function in dogs.

Aminopyrine↗
PubMed1987

Altered liver function in diabetes: model experiments with aminopyrine in the rat.

The aminopyrine breath test is a valuable quantitative liver function test. However, it may be influenced by factors not related primarily to liver disease. For instance, it has been published that diabetes affects microsomal demethylation of aminopyrine in vitro. The relevance of these findings for the in vivo situation, however, is ill defined. Aminopyrine disposition was evaluated, therefore, by performing an in vivo-in vitro comparison of its kinetics in control, diabetic and insulin-treated diabetic rats. Diabetes was induced by streptozotocin (75 mg/kg i.v.). A tracer dose of [14C]aminopyrine was injected i.p. (40 mu Ci/kg, 0.7 mg/kg) and the kinetics of 14CO2 in breath as well as disappearance of aminopyrine in blood were followed simultaneously for 2 hr. Diabetes increased the 14CO2 elimination rate constant in breath by 90%, whereas total recovery of 14CO2 in breath was decreased by 30% (P less than .001). Aminopyrine clearance in blood was doubled in diabetic rats compared to control (48.9 +/- 11.3 vs. 21.4 +/- 3.3 ml/min X kg, P less than .001). This was due to an increased volume of distribution (1.99 +/- 0.31 in diabetic rats vs. 0.96 +/- 0.11 liters/kg in control). In vitro aminopyrine kinetics in hepatic microsomal preparations showed a 52% higher Vmax of aminopyrine demethylase in D (P less than .001), whereas Km remained unchanged. The diabetes-induced changes were reversible by insulin. It is concluded that diabetes alters the aminopyrine breath test by interfering with demethylation rate and distribution of aminopyrine, and by changing the fate of the cleaved C1-fragments.

Aminopyrine↗
PubMedDate not supplied

Reduction of hepatic tetrahydrofolate and inhibition of exhalation of 14CO2 formed from [dimethylamino-14C]aminopyrine in nitrous oxide-treated rats.

The exhalation of 14CO2 after the administration of [dimethylamino-14C]aminopyrine to an organism is assumed to reflect the demethylation of aminopyrine by hepatic mixed-function oxidase activity. The formaldehyde formed as a result of the demethylation of aminopyrine is then sequentially oxidized to formic acid and CO2. The last step in the pathway, i.e., formate oxidation, is dependent upon tetrahydrofolate; thus, factors which alter hepatic tetrahydrofolate potentially may modify 14C-aminopyrine metabolism to 14CO2 in vivo. Exposure of rats to nitrous oxide (N2O) produces a significant reduction in hepatic tetrahydrofolate as a result of the inhibition of 5-methyltetrahydrofolate:homocysteine methyltransferase activity (E.C. 2.1.1.13). In the present study, exposure of rats to N2O/O2 (1:1) for 4 hr prior to the administration of 14C-aminopyrine (40 or 400 mumoles per kg) produced a 60% reduction in the peak rate of 14CO2 exhalation and a 45% decrease in the total 14CO2 exhaled within 2 hr. In control experiments, exposure of rats to nitrogen/O2 (1:1) produced no effect on 14C-aminopyrine metabolism to 14CO2. Administration of methionine (1.3 mmoles per kg) 30 min prior to 14C-aminopyrine administration reversed the inhibition of 14CO2 exhalation and reduction in hepatic tetrahydrofolate observed in N2O-exposed animals. Aminopyrine (400 mumoles per kg) administration to air-breathing rats did not affect the level of urinary formate, but exposure to N2O produced a 40-fold increase. Aminopyrine administration to N2O-exposed rats produced a 75% increase in urinary formate as compared to rats treated with N2O alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗
PubMed1996

Continuous monitoring of 13C-aminopyrine metabolism in rats: effects of cold exposure and noradrenaline.

A system was developed to allow constant monitoring of hepatic cytochrome P450 activity in awake and unrestrained rats. A continuous 13C-aminopyrine perfusion was performed, and breath samples obtained for endogenous CO2 production and 13C measurements, to calculate 13C O2 production due to aminopyrine demthylation. Increasing doses of 13C-aminopyrine produced a hyperbolic increase of expired 13CO2, compatible with an in vivo measurement of enzymatic activity. Acute-cold exposure of the rats during 13C-aminopyrine perfusion produced a two-fold increase of endogenous CO2 production, together with a 27% increased 13C-aminopyrine metabolism (p<0.05 vs basal conditions). In contrast, noradrenaline (20 microg/kg BW/min), despite a similar effect on energy expenditure, did not significantly change 13C-aminopyrine metabolism. Acute-cold exposure is known to stimulate both adrenal catecholamine secretion and the sympathetic nervous system. The observed difference in 13C-aminopyrine demthylation during cold exposure and nonadrenaline perfusion, therefore, could be due to a more specific effect of adrenal catecholamines on liver aminopyrine metabolism. These results suggest the possibility of prolonged in vivo monitoring of liver metabolism pathways such as aminopyrine demethylation, thus allowing the study of drug acute interactions with cytochrome P450 system.

Aminopyrine↗
PubMed1982

The aminopyrine breath test as a measure of liver function. A quantitative description of its metabolic basis in normal subjects.

The APBT is used widely as a measure of liver function. The development of the APBT into a liver function test of greater diagnostic value requires quantitative information on the processes involved in aminopyrine disposition and metabolism in man and on how APBT values reflect changes in these processes. A dual-isotope kinetic study of aminopyrine disposition and metabolism has been carried out on five normal adult subjects. Oral administration of 13C-aminopyrine (2 mg/kg) accompanied by simultaneous intravenous injection of 14C-aminopyrine was followed by serial measurements of aminopyrine and monomethylaminopyrine in plasma and urine over 6 hr. Timed collections of respiratory CO2 were analyzed for the content of excess 13CO2 and for 14CO2. On separate days, an intravenous bolus of 13C-labeled NaHCO3 was administered to obtain estimates of the kinetic parameters of CO2 elimination in each subject. These data were fitted simultaneously to a multicompartmental model that, in addition to providing hitherto unavailable quantitative information, has revealed that (1) demethylation is the major elimination pathway for aminopyrine; (2) a major alternative pathway not involving demethylation exists for monomethylaminopyrine; and (3) only 50% of the labeled carbon generated by demethylation eventually is oxidized to HCO3-. The sensitivity of seven types of APBT scores to 50% reductions in the rates of aminopyrine absorption, metabolism of monomethylaminoantipyrine, intermediate carbon metabolism, and bicarbonate kinetics was evaluated with breath test curves simulated using the APBT model. Every APBT score currently in use was affected by variations in both gastrointestinal output of aminopyrine and bicarbonate kinetics. There is a need for further development of selective scoring methods in the aminopyrine breath test.

Adult↗
PubMed1977

Aminopyrine metabolism in the presence of hyperbilirubinemia due to cholestasis or hepatocellular disease. Combined use of laboratory tests to study disease-induced alterations in drug disposition.

Hepatocellular diseases, such as hepatitis, cirrhosis, or hepatic neoplasm, are associated with impaired metabolism of certain drugs, including aminopyrine, whereas cholestasis produced variable effects on aminopyrine metabolism. Reasons for the variable effects of cholestasis on hepatic aminopyrine metabolism were sought by performing in patients with hyperbilirubinemia the aminopyrine breath test (ABT), which consists of measurements of 14CO2 in breath 2 hr after oral administration of [14C]aminopyrine. Hyperbilirubinemia (total serum bilirubin less than 1.2 mg/100 ml) in these patients was due to hepatocellular disease or cholestasis. The ABT, defined as the percentage of the administered dose of 14C excreted in breath for 2 hr after [14C]aminopyrine administration, was 6.2 +/- 0.8% (mean +/- SD) in 107 control patients with normal total serum bilirubin. The ABT was severely abnormal (less than 3.1%) in 54 of 77 hyperbilirubinemic patients (70%) with hepatocellular disease and normal (greater than 4.5%) in only 5 of these patients (6%). In contrast, the ABT was severely abnormal in only 1 of 40 cases of cholestasis with hyperbilirubinemia and normal in 70% of these patients. Thus, aminopyrine metabolism is normal in most cases of hyperbilirubinemia due to cholestasis and is only rarely severely abnormal in these patients. On the other hand, severe abnormality in aminopyrine metabolism occurs in the majority of patients with hyperbilirubinemia due to hepatocellular disease. It therefore appears that the ABT may be useful in hyperbilirubinemia to distinguish patients with hyperbilirubinemia due to cholestasis form most patients with hyperbilirubinemia due to hepatocellular disease.

Aminopyrine↗
PubMed1989

Effect of adenosine and adenosine analogs on [14C]aminopyrine accumulation by rabbit parietal cells.

Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on [14C]aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. [14C]Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated [14C]aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on [14C]aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased [14C]aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.

2-Chloroadenosine↗
PubMed1978

Reduced drug elimination in congestive heart failure. Studies using aminopyrine as a model drug.

Aminopyrine disposition was studied in 11 patients with congestive heart failure (CHF) and 15 control patients. The aminopyrine metabolic clearance rate was 29.7 +/- 7.1 ml/min (mean +/- SEM) in the patients with CHF and 125.1 +/- 5.7 ml/min (mean +/- SEM) in the control patients (p less than 0.01). The aminopyrine breath test was 2.6 +/- 0.4 per cent (mean +/- SEM) in the patients with CHF and 5.6 +/- 0.3 per cent (mean +/- SEM) in the control subjects (p less than 0.01). Probably due to fluid retention in CHF, the apparent volume of distribution of aminopyrine increased to 63.3 +/- 4.9 liters (mean +/- SEM) in patients with CHF from 43.1 +/- 1.9 liters (mean +/- SEM) in control patients, thereby further impairing aminopyrine elimination in patients with CHF (p less than 0.01). The aminopyrine breath test was measured in a group of eight patients before treatment for an acute episode of CHF and seven to 10 days after initiation of therapy: in each patient clinical improvement was associated with an increased aminopyrine breath test, mean values of aminopyrine breath test increasing from 2.8 per cent before treatment to 5.2 per cent after initiation of treatment (p less than 0.01). These results suggest that in patients with CHF hepatic drug-metabolizing activity is imparied, and the volume of distribution of drugs is increased, with consequent retardation in rates of drug elimination.

Aged↗
PubMed1987

Interrelationship between aminopyrine oxidation and gluconeogenesis in hepatocytes prepared from fructose-pretreated mice.

Aminopyrine oxidation was studied in isolated hepatocytes prepared from 24-h-starved mice (i) after induction of the NADPH-generating malic enzyme and glucose-6-phosphate dehydrogenase, but not the mixed function oxygenases by fructose, (ii) after induction of both mixed function oxygenases and NADPH-generating malic enzyme and glucose-6-phosphate dehydrogenase by phenobarbital and (iii) without any pretreatment. Phenobarbital pretreatment, as expected, increased the rate of aminopyrine oxidation of isolated hepatocytes. However, fructose pretreatment also enhanced the rate of N-demethylation of aminopyrine by more than 100% supporting the view that the availability of NADPH is rate limiting in drug oxidation under certain conditions. The role of malic enzyme and glucose-6-phosphate dehydrogenase in the NADPH supply for aminopyrine oxidation was investigated by the addition of two groups of gluconeogenic precursors: lactate or alanine and glycerol or fructose with the simultaneous measurement of glucose synthesis and aminopyrine N-demethylation. There was a clear correlation between the increased rate of aminopyrine oxidation and the decreases of glucose production caused by aminopyrine. Gluconeogenesis in the presence of 1 mM aminopyrine was decreased by 70-80% when alanine or lactate were used as precursors, it was decreased by only 35-40% when glucose production was started from glycerol or fructose; in an accordance with the facts that NADPH generation and gluconeogenesis starting from alanine or lactate share two common intermediates--malate and glucose-6 phosphate--, while there is only one common intermediate--glucose-6 phosphate--if fructose or glycerol are used. Similar results were obtained with the addition of the structurally dissimilar hexobarbital. It is concluded that besides malic enzyme, glucose-6-phosphate dehydrogenase also takes part in NADPH supply for drug oxidation in glycogen-depleted hepatocytes.

Aminopyrine↗
PubMed1984

Enhancement effects of barbital on the teratogenicity of aminopyrine.

Aminopyrine and its compound with barbital have been used in humans as analgesics and antipyretics. A compound, pyrabital (2 molecules of aminopyrine and 1 molecule of barbital) given daily on Days 9, 10 and 11 of gestation produced significant yields of fetal deaths and malformations in ICR/Jcl mice. Most malformations induced were ruptured omphaloceles (eventration of the abdominal viscera), which were associated with malrotation of the intestine, cleft palates, and tail anomalies, finger and toe anomalies. Aminopyrine also induced significant yields of fetal deaths and malformations. However, the incidence of fetal deaths and malformations induced by a dose of pyrabital was significantly higher than that by an equivalent dose of aminopyrine which was contained in pyrabital. When aminopyrine (0.21 mg/g) and barbital (0.09 mg/g) were given in 2 separate injections to pregnant mice, teratogenicity was approximately equal to that by the equivalent dose of pyrabital (0.3 mg/g). Consequently, potent teratogenicity of pyrabital is not caused by the compound, but only by the coexistence of barbital and aminopyrine. Such enhancement effects of barbital may be due to the induction of enzymes responsible for transforming aminopyrine to teratogenic forms, because pretreatment with barbital and phenobarbital similarly enhanced embryotoxicity of aminopyrine.

Abnormalities, Drug-Induced↗
PubMed1996

Redox mediation in the peroxidase-catalyzed oxidation of aminopyrine: possible implications for drug-drug interactions.

Many drugs, industrial pollutants, and other xenobiotics are known to be oxidized by peroxidases to potentially harmful free-radical intermediates. We have examined the possibility that certain compounds, acting as efficient peroxidase substrates, may stimulate the formation of reactive free radicals by acting as mediators of electron transfer reactions (redox mediators). To explore this hypothesis, we have investigated the interaction of two well-known peroxidase substrates, chlorpromazine and aminopyrine. As shown by ESR and UV-visible spectroscopy, chlorpromazine radical was able to oxidize aminopyrine to aminopyrine cation radical. The rate constant for this rapid, pH-dependent, reaction was estimated to be 1 x 10(7) M-1 s-1 at pH 4.5. Transient-state and steady-state kinetic studies both showed that rate constants for chlorpromazine oxidation to its cation radical by horseradish peroxidase (HRP) were about 100-fold greater than for the corresponding HRP-catalyzed oxidation of aminopyrine to its cation radical. When both aminopyrine and chlorpromazine were present with HRP and H2O2, aminopyrine cation radical formation was stimulated 100-fold. Concomitantly, the accumulation of chlorpromazine cation radical was completely inhibited in the presence of aminopyrine. Similar results were obtained when lactoperoxidase, myeloperoxidase, or the myeloperoxidase mimic HOCl were substituted for HRP. These data suggest that chlorpromazine can act as a redox mediator for peroxidase-catalyzed oxidation of aminopyrine and other chemicals. We suggest that some peroxidase substrates, acting as redox mediators, may stimulate the production of toxic free-radical intermediates from various drugs and other xenobiotics. As such, this may have implications for a number of adverse effects caused by these xenobiotic chemicals.

Aminopyrine↗
PubMed1981

Does gastric aminopyrine clearance reflect gastric mucosal blood flow or parietal cell function?

Gastric aminopyrine clearance was measured in human volunteers and dogs with untreated basal secretion, in human volunteers and dogs treated with secretory inhibitors, in dogs treated with histamine, and in patients with pernicious anaemia. When aminopyrine was given as a bolus to man or dog, aminopyrine clearance and the ratio aminopyrine concentration in gastric juice/aminopyrine concentration in plasma showed an initial peak two to three times over steady state levels. When aminopyrine was given with histamine, the peaks were even higher. No peaks occurred when an aminopyrine bolus was given to patients with pernicious anaemia or to healthy volunteers treated with secretory inhibitors. The height of the peaks paralleled the acid secretory rate. The peaks may best be explained by aminopyrine accumulation in the parietal cells and washing out of aminopyrine by volume flow. The steady state levels might reflect both parietal cell function and gastric mucosal blood flow.

Aged↗
PubMed1982

Aminopyrine accumulation by mammalian gastric glands: an analysis of the technique.

Isolated gastric glands from rabbits and parietal cells from dogs have recently become useful in studying the control and enzymatic mechanisms of gastric H+ secretion. The present studies were performed to determine the experimental variables that account for widely differing aminopyrine accumulation reported in various publications. We found that two principle factors were responsible for wide differences in aminopyrine accumulation. First, we found that commercially available aminopyrine contained an unidentified impurity that increased with storage. A procedure for purification is included. The contaminant is not accumulated in secreting gastric glands and thereby reduces the aminopyrine ratio that can be achieved. Mixing of glands appeared to be the second important variable. It was found that incubation in 1.5-ml capped conical polypropylene centrifuge tubes in the horizontal position with shaking in the long axis of the tubes gave aminopyrine ratios that were more than double the results obtained by other mixing techniques. In addition a gland density of 1--2 mg dry wt/ml glands and a mixing rate of 110 cycles/min gave the best results. Calculations indicate that, at high gland densities, even modest amounts of impurity in the aminopyrine will significantly reduce aminopyrine ratios. With optimal conditions our greatest aminopyrine ratio was 1,050, which suggests an H+ concentration of approximately 67 mM in the canaliculi and tubulovesicular membrane system of the parietal cell. Such a level of function approaches that of the intact in vivo organ.

Aminopyrine↗
PubMed1983

A noninvasive method for the study of hepatic drug metabolism in rodents: aminopyrine metabolism in rats.

A rapid, sensitive, and simple high-performance liquid chromatography method is described for the direct analysis of aminopyrine in saliva. The detection limit was found to be 12 ng/ml of sample. Accuracy and precision were maintained with as little as 1 microliter of saliva. Thus the rate of elimination of aminopyrine has been monitored noninvasively in rats. The aminopyrine half-life was found to be 59.5 +/- 10.5 (SD) min. The half-life was independent of an aminopyrine dose between 50 and 200 mg/kg. In rats single intraperitoneal doses of SKF 525-A (20 mg/kg) produced increases in aminopyrine half-life and salivary aminopyrine concentration. Phenobarbital induction lowered the aminopyrine half-life to 33.2 +/- 8.5 min and the salivary aminopyrine concentration.

Aminopyrine↗
PubMed1988

Induction of anacidity restores gastric aminopyrine clearance in canine hemorrhagic shock.

The determinants of gastric aminopyrine clearance were studied in a canine hemorrhagic shock model. Adult mongrel dogs were anesthetized, and their stomachs perfused with 0.1 N HCl through an esophageal and a duodenal cannula. Blood flow to the serosal layer of the anterior gastric wall was measured by a laser flowmeter. Hemorrhagic shock was induced by controlled arterial bleeding to a mean systolic blood pressure of 40 +/- 5 mm Hg (n = 8), resulting in a 36 +/- 8% drop of gastric wall blood flow. In contrast, the aminopyrine clearance did not reveal the expected drop and remained unchanged during shock. When acid secretion was abolished by intravenous omeprazole (1.3 mg/kg bolus plus 0.75 mg/kg/h infusion), aminopyrine concentrations dropped in the gastric perfusate and rose in the serum during shock, resulting in a similar decrease in the clearance (53 +/- 25%) as compared to the flowmeter readings. In control experiments without hemorrhagic shock, omeprazole did not affect the concentrations of aminopyrine in serum and in the perfusate, or the recovery of 14C-labeled aminopyrine in the mucosa at the end of the experiment. These studies indicate that the aminopyrine clearance is impaired in hemorrhagic shock, and that complete inhibition of acid secretion by omeprazole restores the apparent aminopyrine clearance by divergent effects on blood and gastric juice concentrations of aminopyrine.

Aminopyrine↗
PubMed2004

Kinetic analysis of demethylation of 13C-aminopyrine in healthy dogs.

OBJECTIVE: To describe the kinetics of demethylation of 13C-aminopyrine in healthy dogs for use in determining the most appropriate time for collection of blood samples for a 13C-aminopyrine demethylation blood test for evaluation of hepatic function. ANIMALS: 9 healthy dogs. PROCEDURES: A 2-mL baseline blood sample was collected into an evacuated heparinized tube, and 13C-aminopyrine was administered to each dog (2 mg/kg, IV). Additional 2-mL blood samples were collected 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 240, 300, and 360 minutes after 13C-aminopyrine administration. The CO2 was extracted from blood samples by addition of a strong acid, and the percentage dose of 13CO2 (PCD) in the extracted gas was determined by fractional mass spectrometry. RESULTS: No dogs had gross evidence of adverse effects, and all had an increase in PCD after IV administration of 13C-aminopyrine. The PCD had the least variability among 5 variables used to evaluate hepatic demethylating capacity. Peak PCD was detected at 30 minutes in 1 dog, 45 minutes in 5 dogs, 60 minutes in 2 dogs, and 75 minutes in 1 dog. The mean PCD for the 9 dogs peaked at 45 minutes after 13C-aminopyrine administration. CONCLUSIONS AND CLINICAL RELEVANCE: PCD appears to be the preferable variable for evaluation of hepatic demethylating capacity. Intravenous administration of 13C-aminopyrine leads to a consistent increase in PCD. Mean PCD peaked 45 minutes after administration, suggesting that blood sample collection 45 minutes after 13C-aminopyrine administration may be appropriate for use in estimating hepatic demethylating capacity.

Aminopyrine↗
PubMed1990

The mechanism of myeloperoxidase-catalysed oxidation of aminopyrine.

1. Myeloperoxidase catalysed the H2O2-supported oxidation of aminopyrine in the presence of Cl-, generating the aminopyrine cation radical (AP+.). The rate of AP+. formation was determined by monitoring the absorbance at 565 nm. The pH optimum of the reaction was around 5.0. The rate of AP+. formation increased with increasing concentration of aminopyrine. Inhibition by excess H2O2 was seen at pH 4.5-5.5. 2. When Cl- was replaced by Br-, the rate of AP+. formation increased significantly, and inhibition by H2O2 became less evident and was observed only at pH 5.5. The rate of chemical oxidation of aminopyrine by HOCl was much slower than that by Br2. 3. Compared with the chlorination of monochlorodimedone (MCD), the reaction between aminopyrine and HOCl, produced by the enzymic peroxidation of Cl-, is rate-limiting in the myeloperoxidase-catalysed oxidation of aminopyrine. The differences in kinetic behaviour between the myeloperoxidase-catalysed chlorination of MCD and oxidation of aminopyrine are explained by the low reactivity of HOCl towards aminopyrine.

Aminopyrine↗