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T Talseth

Publications and source records attributed to T Talseth.

84 records · Page 5Linked to original sources
PubMed1977

Kinetics of hydralazine elimination.

Hydralazine was given orally in single doses of 10, 25, and 50 mg to 2 slow-acetylating subjects, while 2 rapid-acetylating subjects also received 100- and 150-mg doses on different occasions. Administration of the 50-mg dose to the subjects who were slow acetylators and the 150-mg dose to those who were rapid acetylators caused a disproportionately large increase in the amount of unchanged drug appearing in the systemic circulation as judged from the increases in the ratios of areas under concentration-time curves (AUC) to dose. A modification of the gas-liquid chromatographic hydralazine assay allowed the simultaneous determination of hydralazine and its acetylated metabolite, 3-methyl-s-triazolo-3,4,a-phthalazine (MTP), in serum. It was found that the disproportionately large increases in the AUC/dose ratio of hydralazine upon intake of 50 or 150-mg doses by the slow and rapid-acetylating subjects, respectively, were paralleled by a decrease in the ratio AUCMTP/AUChydralazine during a 6-hr observation period. It is concluded that the acetylation of hydralazine in man is a capacity-limited process.

Acetylation↗
PubMed1977

Polymorphic acetylation of sulphadimidine in normal and uraemic man.

After oral administration of sulphadimidine (mean dose 3.33 g) to 21 volunteers it was possible to distinguish fast and slow acetylators by calculating the acetylated fraction (%acSDD) in a single serum sample obtained at any time between 1/2-24 h. There was a close correlation between %acSDD in serum and in urine collected from 0-8 h. Two groups of patients with chronic renal failure were studied. Four of the first 8 patients studied would have been designated as slow acetylators from their low %acSDD in 0-8 h urine, but as fast acetylators from their %acSDD in serum 6 h after drug administration. The next 18 patients were given a smaller dose of SDD (2 g) and they showed complete intra-individual correlation between %acSDD in 0-24 h urine and in a serum sample obtained at 24 h. The patients could be divided into 2 sub-groups on the basis of %acSDD in serum and urine, thus demonstrating the ability of this procedure to distinguish fast and slow acetylators, even in advanced chronic renal failure.

Acetylation↗
PubMed1976

Studies on hydralazine. II. Elimination rate and steady-state concentration in patients with impaired renal function.

Following a single 50 mg dose of hydralazine (Apresoline) in 13 patients with impaired renal function, a decrease in glomerular filtration rate (GFR) was correlated with an increase in serum half-life (T1/2) of the drug (r=-0.69; p less than 0.01). The T1/2 was 15.8 h in one patient with a GFR of 16 ml-min-1, as compared to a T1/2 of 1.7-3.0 h found previously in 16 healthy volunteers. In 49 patients on long-term antihypertensive treatment with hydralazine, the ratio between the minimum steady-state drug concentration and the daily dose of hydralazine (Cminss : Dose) increased as the GFR decreased. This accumulation of the drug was particularly evident in patients with a GFR less than 30 ml-min-1 (r=-0.63; p less than 0.01; n=19). As renal excretion of unchanged hydralazine is generally regarded as unimportant, the slower elimination rate in chronic renal failure was probably caused by a slower rate of metabolic conversion. It was found, however, that the renal excretion of hydralazine could easily have been underestimated, as only 12.7% of an initial hydralazine concentration of 200 ng-ml-1 in urine could be recovered after storage of the samples at room temperature for 24 h.

Dose-Response Relationship, Drug↗
PubMed1976

Studies on hydralazine. III. Bioavailability of hydralazine in man.

The bioavailability of orally administered hydralazine was assessed in 4 healthy subjects after separate administration of a single oral or intravenous dose (0.3 mg-kg-1). Comparison of the areas under the serum concentration-time curves showed that 26-55% of the oral dose was available to the systemic circulation as unchanged drug. The 0-24 h excretion of the drug in urine was rapid: 11.4-14.1% of the dose after intravenous administration, and 2.0-3.6% after an oral dose. Acetylation of hydralazine leads to formation of 3-methyl-s-triazolo-3,4, aphthalazine (MTP) and a gas-liquid-chromatographic method for its measurement in urine was developed. After oral and intravenous administration, 0.8-1.2% and 1.4-2.3% of the dose, respectively, were recovered within 24 hours from urine as MTP. After oral administration there was a relative increase in the amount of MTP in every subject, which indicates route-dependent metabolism. The lower bioavailability of oral hydralazine could be explained in terms of first-pass metabolism.

Acetylation↗
PubMed1976

Isolated gastric involvement in Crohn's disease. Report of a case simulating scirrhus carcinoma.

A 63-year-old woman suffered a short period of nausea and vomiting. X-ray examination of the upper gastrointestinal tract was suspicious of scirrhus carcinoma of the stomach. At operation the suspicion was strengthened, and total gastrectomy was performed. Microscopic examination showed chronic, granulomatous gastritis compatible with Crohn's disease. The patient died on the 8th day postoperatively with caval thrombosis obliterating the inlet to the right auricle. No other localization of the disease could be demonstrated on thorough microscopic and macroscopic examination of the whole gastrointestinal tract.

Adenocarcinoma, Scirrhous↗
PubMed1970

[Breast neoplasms].

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Breast Neoplasms↗
PubMedDate not supplied

Hypotensive effect of the hydralazine--acetone hydrazone in conscious rabbits: evidence for its back-conversion to hydralazine in vivo.

The hydralazine--acetone hydrazone (HAH) has previously been identified as a metabolite of hydralazine (H) in humans. We compared the hypotensive effects of HAH and H in groups of hypertensive rabbits. Both compounds caused a dose-dependent depressor response, with a potency ratio of HAH to H of approximately 0.2. Upon their intravenous administration to anephric rabbits, both H and HAH produced sustained concentrations in plasma of the H-pyruvic acid hydrazone, demonstrating that back-conversion of HAH to H occurred in vivo. We conclude that HAH is hydrolyzed in vivo to yield parent H. The levels of the H-metabolite, the pyruvic acid hydrazone, suggest that the hypotensive effect of HAH could be explained entirely by generation of H in vivo. This combined pharmacokinetic and pharmacodynamic approach can be applied to other H-hydrazones to evaluate their backconversion to H in vivo.

Animals↗
PubMedDate not supplied

Studies in the rabbit on 3-methyltriazolophthalazine, an acetylated metabolite of hydralazine. Evidence for an alternative route of formation.

The formation and disposition of 3-methyltriazolophthalazine (MTP), an acetylated metabolite of hydralazine (H) was studied in rabbits. Following its iv administration MTP was rapidly and almost completely metabolized. The major metabolite in plasma and urine was found to be a hitherto unrecognized glucuronide conjugate, most likely of the carboxylic acid analogue of MTP. The hydralazine-pyruvic acid hydrazone (HPH), which is a major plasma metabolite of H, was recognized as a more potent source for MPT in vivo than was parent H. MTP was also formed in significant amounts in vitro following incubation of HPH in phosphate buffer. We conclude that MTP can arise directly from HPH. Consequently, MTP and the compounds formed during its further biotransformation may not provide any valid measure of the extent to which H is acetylated in vivo.

Animals↗