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PubMed1967

A comparison of the effects of tolazamide and tolbutamide upon blood glucose and serum insulin and lipid levels in diabetic subjects.

The effects of tolazamide (300 mg. daily), a new oral hypoglycemic sulfonylurea, and tolbutamide on the blood glucose, serum insulin, cholesterol and triglyceride levels were compared in 14 subjects with maturity-onset diabetes of varying severity. The mean effects of the two drugs in the pharmacologically equivalent doses were the same. In particular, the mean reduction of the blood glucose level was 19% and of the serum triglyceride level was 17% with both agents. However, an individual subject might respond to one agent and not to the other; neither the blood glucose nor the serum lipid response could be predicted from the pretreatment blood glucose level or the per cent of ideal body weight.

Adult↗
PubMed1980

Effect of alphamethyldopa on the half-lives of antipyrine, tolbutamide and D-glucaric acid excretion in man.

Alphamethyldopa has been found to prolong the biological half-lives of Antipyrine and Tolbutamide and to decrease D-glucaric acid excretion in man. These observations suggest that the liver microsomal enzyme system metabolizing drug in man is inhibited by alphamethyldopa. No side effects were found during treatment with alphamethyldopa at the dose levels used in this study.

Adult↗
PubMedDate not supplied

Kinetic analysis of tolbutamide-sulfonamide interaction in rabbits based on clearance concept. Prediction of species difference from in vitro plasma protein binding and metabolism.

The interaction between tolbutamide (TB) and sulfonamide (SA) in rabbits was quantitatively investigated by both in vivo and in vitro experiments, and the mechanisms of species difference between rabbits and rats were analyzed by comparing the two total body clearances (CLtot) obtained from in vivo and in vitro studies. The sulfonamides used were sulfaphenazole (SP) and sulfadimethoxine (SDM). In vivo CLtot of TB was changed little by SA in rabbits, which was contrary to the phenomenon seen in rats, i.e. CLtot was markedly decreased by SA in rats (Sugita et al., Biochem. Pharmacol., 30, 3347, 1981). The total body clearance defined as CL in vitro tot.pred was predicted for TB in the presence and absence of SA by the equation: CL in vitro tot.pred congruent to fB CL in vitro int, where fB is the blood-free fraction and CL in vitro int is the hepatic intrinsic clearance of unbound drug obtained from in vitro experiments using liver microsomal fraction. A comparatively good agreement was observed between the two CLtot obtained from in vivo and in vitro data. The analysis in rabbits based on these in vitro experiments showed that the small gross changes of in vivo CLtot induced by SA were due to the compensative changes of two factors, i.e. fB and CL in vitro int which in the presence of SA were approximately 200 and 50% of the control, respectively. However, in rats, the marked decrease of in vivo CLtot induced by SA was explained by the greater degree of the decrease in CL in vitro int than that of the increase in fB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Comparative metabolism of tolbutamide by isolated hepatocytes from rat, rabbit, dog, and squirrel monkey.

Tolbutamide (TB; 1-butyl-3-p-tolylsulfonylurea) was used for metabolism studies with hepatocytes isolated from the rat, rabbit, dog, and squirrel monkey to validate their usefulness as models for comparative in vivo metabolism. Hepatocytes were prepared by whole liver or biopsy perfusion. TB (3 X 10(-4) M) was metabolized by each of the preparations over a 4-hr incubation period at rates ranging from 175.8 to 9.2 pmol/10(6) cells/min with the rates from hepatocytes from: rat greater than rabbit much greater than squirrel monkey greater than dog. The metabolite profiles determined in extracts of hepatocyte suspensions after 4 hr of incubation showed marked species differences. The major metabolite for the rat and squirrel monkey was 1-butyl-3-p-hydroxy-methylphenylsulfonylurea (73.2 and 46.7% of total metabolites, respectively). p-Tolylsulfonylurea and p-tolylsulfonamide were the major metabolites found in the dog (44.1 and 40.2%, respectively). Rabbit hepatocytes formed mostly 1-butyl-3-p-carboxyphenylsulfonylurea (63.9%). Both the relative rates of metabolism and the metabolite profiles from hepatocytes from the rat, rabbit, and dog correlated well with published in vivo data on TB plasma half-lives and urinary metabolite profiles. These results suggest that isolated hepatocytes may have utility as in vitro models for comparative in vivo metabolism.

Animals↗
PubMedDate not supplied

Effect of refeeding after starvation on basal and tolbutamide-stimulated insulin secretion and beta-adrenergic receptor function in the regulation of insulin release and lipolysis in obese patients.

Serum insulin, blood glucose and plasma free fatty acids (FFA) were determined in 14 subjects with a simple obesity under basal conditions and during the tests with tolbutamide, propranolol and epinephrine before and after fasting of 14 days duration, on restricted diet of 1300 kcal. After refeeding some changes in pancreatic B cells reactivity and an altered metabolic responsiveness to epinephrine and propranolol were found as compared to prefasting values. It may be concluded that after refeeding a further increment of beta-adrenergic function seems to contribute to accelerated lipid mobilisation and partly to increased insulin secretion.

Adult↗
PubMed1982

[Influence of (+)-Catechin and Dithiocarb on the Pharmacokinetics of Phenprocoumon, Tolbutamide and Three Inhalation Anesthetics in rats].

Pretreatment with (+)-catechin ((+)-cyanidanol-3, Catergen) (200 mg/kg p.o.) did not alter the elimination of intravenously injected phenprocoumon (0.6 mg/kg) or tolbutamide (100 mg/kg) in rats, while dithiocarb (Sodium diethyl-dithiocarbamate) (200 mg/kg p.o.) prolonged only the elimination half-life of phenprocoumon to a small extent. The metabolism of halothane (100 ppm), enflurane (100 ppm) or methoxyflurane (300 ppm) was studied by measuring the disappearance of the compounds from the atmosphere of a closed exposure system. Pretreatment with (+)-catechin did not impair the metabolic removal of all three anesthetics; in the case of enflurane (+)-catechin caused a small, but significant shortening of the elimination half-life, for enflurane and methoxyflurane the uptake of the compounds into the rats seemed to be impaired under the influence of (+)-catechin. Dithiocarb strongly impaired the in vivo metabolism of halothane and methoxyflurane, whereas that of enflurane remained unaffected.

4-Hydroxycoumarins↗
PubMed1983

[Action of alkaloids from podophyllin on the response of pancreatic beta-cells of the rabbit to tolbutamide].

Some antineoplastic agents alter the microtubular-microfilamentous system involved in insulin release. The authors studied the effect of the podophyllotoxin derivate VM-26 and the epipodophyllotoxin derivative VP-16-213 on the insulin release by the pancreatic beta-cell after tolbutamide stimulation. VP-16-213 produced a slowing and partial inhibition of insulin release, and VM-26 inhibited the late stage of insulin release.

Animals↗
PubMed1982

[Hyperinsulinism and insulin resistance in the polycystic ovary syndrome as tested with tolbutamide].

The aim of this research was to study both insulin secretion and insulin resistance index (IRI) in seventeen females, aged 16-30, affected by polycystic ovarian syndrome. The diagnosis was made using clinical, hormonal, radiological and echographic criteria. Eight healthy women, carefully matched with our patients for age and for statistical obesity incidence, were studied as controls. Both glycemic and insulinemic curves, areas, insulinemic/glycemic area ratio (IRI) were studied by tolbutamide test (1 g i.v.). Areas were assessed by planimeter, blood glucose by Trinder method, blood insulin by a RIA method, statistical study by t Student test and correlation coefficients. These latter were determined by comparing individual plasma testosterone, FSH, LH and LH/FSH ratio values together with urinary total 17-ketosteroid and delta HEA output values on the one hand and insulin areas and IRI values on the other. Increased glycemic areas, insulinemic peaks and areas, associated with markedly increased IRI values, were observed in the patients. A correlation exists between hyperinsulinism, insulin resistance on the one hand and increased urinary androgens output on the other. delta HEA resulted particularly increased over other androgenic fractions.

Adolescent↗
PubMed1980

[Contribution to the analysis of the hypoglycaemic agent tolbutamide. Part 2 (author's transl)].

The chemical identification reaction for tolbutamide (USP 1975) involves its hydrolysis by sulphuric acid with the formation of n-butylamine. This amine then reacts with diazotised p-nitraniline to give 8 red or yellow coloured compounds. A radicalic and an ionic mechanism for their formation, which are partially interrelated, are discussed. Other oral sulphonamide-hypoglycaemic agents give a positive result with this identification reaction.

Chemical Phenomena↗
PubMed1995

Kinetics of drug metabolism in rat liver slices. Rates of oxidation of ethoxycoumarin and tolbutamide, examples of high- and low-clearance compounds.

Ethoxycoumarin (EC) and tolbutamide (TOL) were selected as examples of high- and low-clearance drugs, respectively, to investigate suitable methodologies for obtaining kinetic data on metabolism by precision-cut rat liver slices. A number of characteristics of the slice incubation were compound-dependent. TOL showed linear rates of metabolism over a longer time period than EC and was insensitive to the method of incubation (rotating vials and gyrating culture plates). Also, the need for complete tissue disruption (e.g. via sonication) before analysis was essential for EC but unimportant for TOL. This may suggest that conjugates do not freely diffuse out of the liver slice unlike oxidative metabolites. Both drugs showed rates of metabolism that were dependent on slice thickness (150-530 microns). A high turnover (intrinsic clearance 7.9 microliters/min) and low KM (1.3 microM) for EC, and a low turnover (intrinsic clearance 0.8 microliter/min) and high KM (707 microM) for TOL were determined in slices. These differences in kinetic behavior are comparable with those seen in hepatic microsomes, freshly isolated hepatocytes, and in vivo.

Animals↗
PubMed1975

Kinetics of the early insulin response of the perfused rat pancreas to various metabolites and tolbutamide.

The collection every 15 seconds of the portal effluent of the isolated and perfused rat pancreas permitted the following observations: while the insulin response to tolbutamide (250 or 125 mug/ml) occurred immediately, that to glucose (15 mM), or to 1-leucine (15 mM) was delayed by 60-90 seconds. The response to d-glyceraldehyde occurred slightly but significantly more quickly than that of glucose. The response to alpha-keto-isocaproate was an intense and immediate one. Isovalerate elicited no insulin discharge. These results suggest that d-glucose and l-leucine have to be metabolized to stimulate insulin secretion and that alpha-keto-isocaproate seems to be a direct and specific signal.

Animals↗
PubMed1976

[A method of studying insulin secretion in humans: the glucose stimulation test, followed by tolbutamide].

Various parameters of the insulin secretion in man may be appreciated and calculated by studying the insulin response to an intravenous pulse of glucose followed 120 minutes later by one of tolbutamide. The relative insensitivity of the B cell to glucose, probable marker of a constitutional pancreatic predisposition to diabetes may be assessed in a given individual whatever his age and body weight. The glucose intolerance per se is due to, or accompagnied by various B cell dysfunctions according to its etiology. This is illustrated by the results observed in chronic pancreatitis, liver cirrhosis, aged or obese subjects.

Age Factors↗
PubMedDate not supplied

[Dynamics of the content of immunoreactive insulin and sugar in the blood during tests with glucose, tolbutamide and leucine in patients with Cushing's syndrome].

This work was aimed at the study of reserve capacities of the insular apparatus of the pancreas during the glucose tolerance test, and the test with tolbutamide and leucine in patients with Itsenko-Cushing's disease. The mentioned patients showed an increase in the immunoreactive insulin (IRI) level on the fasting stomach and a fall of the regulatory capacities of the insular apparatus of the pancreas; this was expressed in a later and high increase in the IRI level during the tests.

17-Hydroxycorticosteroids↗
PubMed1977

Comparative hypoglycemic and hypoketonemic effects of tolbutamide and glypentide in rat.

Fed and 24 h fasted rats were treated by stomach tube with different doses of either tolbutamide or gluypentide and they were compared with controls treated with placebo. At low doses glypentide was ten times more effective as hypoglycemic agent than tolbultamide whereas it was only twice as effective in the fasted rats. Supramaximal doses of either drug produced the same effect decreasing blood glucose levels. Both drugs were able to decrease the rise of blood ketones in fasted rats, but the comparative effect was not parallel to the one observed on glycemia and not proportional to the doses used. The different responses are interpreted as function of the hypoglycemic effect, which would be mainly mediated through the insulinotropic action of these drugs, while the hypoketonemic would be the result of both their insulinotropic effect and their direct action on lipolysis and ketogenesis.

Animals↗
PubMed1976

Glycemia and plasma IRI level after tolbutamide in hyposomatrophic dwarfs treated with HGH.

The insulinogenic function of the pancreatic islets was assessed by the use of tolbutamide stimulation in 25 children with hyposomatotrophic dwarfism (HSD). The authors suggest that the low insulin release and/or synthesis is responsible for slight growth response of these children to HGH treatment. There may also be a causative relation between this low insulin response and the tendency of children with HSD to develop diabetes after HGH treatment.

Adolescent↗