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Biomedical subjects

T Talseth

Publications and source records attributed to T Talseth.

At least 73 records · Page 4Linked to original sources
PubMed1983

Acute effects of intravenous cimetidine upon gastric secretion in patients with impaired renal function.

Gastric secretion (volume, pepsin and acid output) was measured in the basal state and during graded doses of intravenous pentagastrin (0.02, 0.2 and 2 micrograms/kg/h) in 5 patients with moderate to severe renal failure. On one occasion they also received intravenous cimetidine (1.5 mg/kg bolus followed by 0.5 mg/kg/h). Sustained cimetidine concentrations of approximately 2 micrograms/ml (8 nmol/ml) were associated with a 75-90% inhibition of stimulated acid output, reflecting both a reduction in volume and a lower acid concentration. Pepsin output was less depressed by cimetidine, as the pepsin concentration of the gastric juice actually increased in response to combined pentagastrin and cimetidine administration. It is concluded that renal failure, although affecting cimetidine pharmacokinetics, does not appreciably alter the response to the drug.

Adult↗
PubMed1983

Effect of cimetidine on intrinsic factor secretion stimulated by different doses of pentagastrin in patients with impaired renal function.

Gastric intrinsic factor (IF) secretion was examined in five patients with impaired renal function during stepwise increasing doses (0.02, 0.2, and 2.0 micrograms/kg/h) of intravenous infusion of pentagastrin alone or in combination with continuous intravenous infusion of cimetidine (05 mg/kg/h) after and initial bolus of 1.5 mg/kg. Whereas cimetidine caused a moderate reduction of maximally stimulated IF output, the output during submaximal stimulation was reduced to basal levels by cimetidine. The results suggest that IF insufficiency may occur during cimetidine treatment in patients with impaired renal function on long-term treatment with H2-blockers.

Adult↗
PubMed1982

Endogenous generation of hydralazine from labile hydralazine hydrazones.

The hypothesis that the pharmacologically active hydralazine hydrazones (HH) are endogenously hydrolyzed to parent hydralazine (H) was tested in a series of in vitro and in vivo systems. The stable hydrazones H alpha-ketoglutaric acid hydrazone and H pyruvic acid hydrazone did not hydrolyze to H in vitro (buffer or plasma), were inactive in vivo and did not generate urinary metabolites of parent H. By contrast, the labile HH, H acetaldehyde hydrazone and acetone hydrazone (HAH) generated H in vitro. H acetaldehyde hydrazone produced in vitro effects that were equipotent to the H concentration measured in the dose solutions. When administered to conscious rats and rabbits, the labile hydrazones reduced blood pressure. This effect was more gradual in onset than that of H. The hypotensive effects of HH were significantly greater than predicted by the amount of H contained in the dose solutions. Metabolic studies were conducted with the labile HH, HAH. After administration of HAH to rabbits, the proportional excretion of the urinary H metabolite, H pyruric acid hydrazone, was equal to that observed after the administration of H. We conclude that HH are inactive, except when hydrolyzed to H. The hydrolysis of certain HH, including HAH and H acetaldehyde hydrazone, in vivo may be nearly complete. Differences in the pharmacodynamic properties between labile HH and H may be related to the time course of generation of H, sequestration of hydrolysis in physiologically inactive sites or other unrecognized mechanisms.

Animals↗
PubMed1981

Aging, cigarette smoking and oral theophylline requirement.

In a prospective study in 73 patients with obstructive pulmonary disease, aged 63.5 +/- 13.5 years (SD), it was found that theophylline dose, cigarette smoking and age were all significant determinants of the steady-state trough plasma theophylline level during oral administration of the drug. As the predictive efficiency of the three factors combined amounted only to 25%, firm dosage recommendations cannot be made. Even among elderly patients, tobacco smokers had significantly lower plasma concentrations of theophylline. It is suggested that in order to obtain trough plasma concentrations of 50 mumol/l (approximately equal to 9 micrograms/ml), a non-smoking 50 year-old patient would require 9.8 mg/kg/day of oral theophylline, the dose increasing to 14.2 mg/kg/day in smokers of the same age. These doses should probably be reduced by 15-20% in 75 year-old patients.

Administration, Oral↗
PubMed1981

Individualization of oral theophylline dosage in elderly patients.

The present study is a prospective evaluation of a dosing nomogram for oral theophylline in 69 middle-aged and elderly patients (mean age 58.5 +/- 15.4 years) with obstructive lung disease. The main features of the nomogram were that the theophylline dose was increased in middle-aged as compared to old patients, and that smokers were always prescribed a higher dose than non-smokers of a similar age. The target theophylline concentration is presently defined as a trough level at steady state of 50 micromol/l. Approximately 50% of the patients achieved theophylline levels within +/- 20% of the target concentration, and none had theophylline levels exceeding 110 micromol/l. We conclude that the nomogram represents a useful guide in establishing a safe initial theophylline dose in this patient group.

Administration, Oral↗
PubMed1980

Quantitative analysis of hydralazine pyruvic acid hydrazone, the major plasma metabolite of hydralazine.

A specific, high-performance liquid chromatographic technique for the measurement of hydralazine pyruvic acid hydrazone is described. This method utilized reversed-phase chromatography for the separation of this hydrophilic metabolite of hydralazine from other fluid constituents present in serum, plasma, or urine of human volunteers and rabbits receiving hydralazine. Detection of the compound of interest is accomplished spectrophotometrically at 250 nm.

Animals↗
PubMed1980

Route and rate of hydrallazine administration as determinants to its hypotensive effect in rabbits.

1. The cardiovascular responses to varying doses of hydrallazine were studied in renal hypertensive rabbits. 2. The depressor effect of hydrallazine was independent of the rate of its i.v. administration (bolus v. a 15 min constant infusion). 3. Intraperitoneally administered hydrallazine was significantly less active than equimolar i.v. doses, and the relative potency (i.p. v. i.v.) did not increase with increasing doses. 4. In spite of inferential evidence to the contrary, we did not find any pharmacodynamic support for non-linear processes being involved in metabolism of hydrallazine.

Animals↗
PubMed1979

Pharmacokinetics and cardiovascular effects in rabbits of a major hydralazine metabolite, the hydralazine pyruvic-acid hydrazone.

The hydrazone of hydralazine and pyruvic acid (HPH) has been recognized as a quantitatively important metabolite of hydralazine in human plasma. We evaluated the disposition of [14C] HPH after its i.v. administration to normal, anephric and probenecid-pretreated rabbits. Renal clearance of HPH in normal rabbits exceeded the glomerular filtration rate by a factor of 3 to 4 and accounted for 80 to 90% of the total body clearance. Active tubular secretion was established by the effect of probenecid pretreatment to reduce the renal clearance of HPH by 80%. Total body clearance of HPH in anephric rabbits was 10% of that of normal animals, emphasizing the minor importance of metabolic conversion for the overall disposition of HPH. HPH in a maximum dose of 50 mumol/kg i.v. had no hypotensive effect in renal hypertensive rabbits and did not interfere with the subsequent hypotensive response to hydralazine. This HPH dose produced plasma levels at least 50 times in excess of those reported in humans after administration of therapeutic doses of parent hydralazine. HPH is consequently of negligible clinical significance, despite the relatively high plasma concentration of this metabolite which occurs after administration of parent hydralazine.

Animals↗
PubMed1979

Pharmacokinetics of hydralazine, apparent hydralazine and hydralazine pyruvic acid hydrazone in humans.

Hydralazine is an antihypertensive vasodilator agent. Lack of specific assay techniques for its measurement have delayed elucidation of its pharmacokinetic profile. This study compares the plasma profiles of hydralazine, measured both by a specific and by a previously published nonspecific assay and of a major plasma metabolite, hydralazine pyruvic acid hydrazone. After po and iv administration of hydralazine, peak hydralazine levels were lower (7-33%) and plasma half lives were shorter (15-31%) when measured by the specific technique. The mean plasma half life of the pyruvic acid hydrazone was 156 min and mean urinary clearance, 28 ml/min. The plasma profile of hydralazine and of the major metabolite, the pyruvic acid hydrazone, do not appear to correspond to the duration of antihypertensive effect of administered hydralazine.

Acetylation↗
PubMed1979

Clinical and pharmacological observations on a new microcrystalline theophylline preparation.

Tablets containing 250 mg of microcrystalline theophylline were given at 6-hourly intervals for 6 days. Minimum plasma theophylline concentrations in eight patients averaged 36.6 +/- 5.4 mumol/l (1 mumol = 0.18 mg), and the corresponding maximum concentration were 81.8 +/- 10.6 mumol/l. In 11 patients, studied after a single 250 mg dose, significant improvements in PEF and FEV1 were observed, in spite of maximum concentrations averaging only 38.8 +/- 2.2 mumol/l, which is below the commonly regarded lower limits of the therapeutic range. Nine of the 11 patients complained of side effects and in three patients a reduction in dose was necessary. In four volunteers given a single dose of 250 mg the plasma concentration of theophylline were not particularly affected by whether the tablets were taken fasting or postprandial.

Adult↗
PubMed1978

Inflammatory tumours in the rectum clinically simulating cancer.

Four patients were admitted to our department after discovery of a palpable mass in the rectal ampulla. All lesions were clinically interpreted as malignant neoplasms. Repeated examinations with biopsies showed nonspecific, inflammatory tumours in all cases. Inflammatory tumours of the rectum may occur in a number of diseases. The lesions in two patients may have their origin in the solitary ulcer of the rectum or colitis cystica profunda, while this diagnosis for certain was made in the fourth patient. The third described patient had a palpable mass in the rectal ampulla after a difficult urethral dilatation, and the mass gradually subsided without treatment. The clinical misinterpretation of inflammatory tumours as malignant neoplasms has been responsible for a considerable number of unnecessary surgical procedures.

Adult↗