Biomedical subjects

L M Hofmann

Publications and source records attributed to L M Hofmann.

At least 19 recordsLinked to original sources

PubMed1987

A randomized study of two preparations for large bowel radiology.

A randomized study was carried out in 195 out-patients, due to undergo large bowel radiological examination, to compare the efficacy, patient acceptance and incidence of side-effects of a commercially-available bowel evacuant kit (magnesium citrate oral solution, phenolphthalein tablets and a bisacodyl suppository) and castor oil with enemas. Overall evaluation by a radiologist of large bowel preparation, based on post-barium evacuation X-rays, was satisfactory in more than 98% of patients while bowel cleanliness, as determined by the ability to detect a 1 cm lesion, was adequate in 95% of patients using either preparation. Patient acceptance was in favour of the commercial preparation in that fewer patients using it found the procedure uncomfortable or indicated a preference for another evacuant than did those prepared with castor oil and enemas.

Adult↗

PubMed1977

Synthesis and antimineralocorticoid activities of some 6-substituted 7 alpha-carboalkoxy steroidal spirolactones.

Several analogues of the previously reported steroidal spirolactone 1a were synthesized. These analogues bear C-6 substituents and include the 6beta-deuterio (1c), the 6beta-bromo (1d), the 6beta-methyl (1e), and the 6alpha-methyl (7) compounds. The 6beta-hydroxy compound 1b, a human and animal metabolite of 1a, was also synthesized. On subcutaneous administration to adrenalectomized rats, all these compounds exhibited the ability to block the effects of administered deoxycorticosterone acetate (DCA) (MED less than or equal to 0.58 mg). Only 7 failed to show anti-DCA effects at the standard test level on oral administration. None was significantly superior in potency to the parent compound 1a.

Adrenalectomy↗

PubMed1977

Aldosterone antagonism studies in the rhesus monkey.

Renal studies in femal rhesus monkeys indicated that 10 micron g was an optimum i.m. sodium-retaining dose of aldosterone. Aldosterone was injected i.m. at dosages of 2.5, 5, 10 and 20 micron g/animal. The 10-micron g dose induced about a 50% reduction in sodium excretion (from 3.7 to 1.7 mEq/6 hr) and was selected as the standard dose for antagonism studies. K excretion and urine volume remained unchanged. Subsequently, the oral antialdosterone activities of spironolactone and canrenone, a delta6 metabolite, were assessed at dosages of 1, 4 and 8 mg/kg. Dose-related increases in the aldosterone-depressed urinary Na/k ratio occurred primarily as a consequence of enhanced sodium excretion. Canrenone possessed antialdosterone potency equal to that of spironolactone. In the absence of exogenous aldosterone, spironolactone (16 mg/kg) was essentially devoid of diuretic activity whereas hydrochlorothiazide (1 mg/kg) induced marked increases in Na (256%) and K (105%) excretion and urine volume (109%).

Administration, Oral↗

PubMed1977

Mexrenoate potassium: a steroidal aldosterone antagonist and antihypertensive.

Mexrenoate potassium (SC-26714) is a water soluble salt of a steroidal hydroxy acid which has been shown to antagonize the sodium-retaining effects of aldosterone at oral dosages of 1 mg/kg and about 1.8 mg/kg in the dog and rat, respectively. Dose-related natriuretic responses, indexed as a reversal (increases) in the aldosterone-depressed urinary log Na/K ratio, indicated that mexrenoate was between 2.1 (dog) and 4.5 (rat) times as potent as spironolactone. Based on sodium output, in intact rats, mexrenoate was essentially inactive as a diuretic with an estimated potency of less than 0.4% that of hydrochlorothiazide. Diuretic potency was not indicative of antihypertensive potency. In dogs with established hypertension (Page model with the remaining kidney decapsulated and cellophane wrapped) both mexrenoate and spironolactone exhibited equivalent antihypertensive responses. An optimum oral dose of either compound was 5 mg/kg/day. Initial and maximum antihypertensive responses were observed on the 2nd and 5th days of treatment, respectively. Recovery to pretreatment hypertensive levels was observed 72 hours later. Mexrenoate shares with spironolactone the pharmacological characteristics of an aldosterone antagonist.

Androstenols↗

PubMed1976

Binding of spirolactones to human plasma proteins.

The lipophilicity and plasma binding of 16 spirolactones and 4 hydroxy acid analogs were determined. Mathematical expressions were derived to correlate quantitatively the extent of plasma binding to the lipophilicity of the drugs. The nonspecific binding of these spirolactones and their hydroxy acid analogs was also analyzed using purified serum albumin. A computer program was developed to examine the mechanism of drug-serum protein interactions. One class of binding sites was observed for the range of concentrations used. The number of binding sites and the equilibrium binding constant were computed and were sensitive to substitution at the C-6 and C7 positions. Hydrolysis of the C-17 lactone ring in spirolactones to form hydroxy acid analogs resulted in a decrease in the lipophilicity and, hence, the equilibrium constant for binding.

Binding Sites↗

PubMed1976

Synthesis and antimineralocorticoid activities of some 7alpha-cyano and 7alpha-alkoxycarbonylamino steroidal spirolactones.

The synthesis and antimineralocorticoid potencies of several steroidal spirolactones bearing novel nitrogenous substituents in the 7alpha position are reported. These substituents include the cyano, the isocyanato, and the alkoxycarbonylamino groupings. The nitrile 1b and the N-carbomethoxy compound 1h showed good antimineralocorticoid potency (MED less than or equal to 0.79 mg) on subcutaneous administration to adrenalectomized rats.

Adrenal Glands↗

PubMed1975

Renal clearance of canrenoate in normal man.

Potassium canrenoate was administered intravenously, twice at a 9-hr interval, to 3 apparently healthy male volunteers. No consistent changes in endogenous creatinine or PAH clearances were observed for 6 hr after the initial 200-mg dose of this aldosterone antagonist. The clearance of canrenone (the major gamma-lactone metabolite) exceeded by 70% the simultaneous clearance of creatinine from the second through the sixth hour. The excretion of canrenone amounted to 6.8 mg (3.4%) of the dose during the 6-hr clearance study, but was nearly absent (0.2 mg) during the ensuing 6- to 9-hr period. The cumulative excretion of the glucuronide conjugate of canrenone amounted to 4.6 and 2.8 mg (2.3% and 1.4%) of the dose during these respective periods. A sustained retention of K was observed in 1 subject. Otherwise, as was anticipated in the absence of hyperaldosteronism, urinary electrolyte levels were essentially unchanged. Circulating aldosterone and plasma renin activity levels were essentially unaltered.

17-Ketosteroids↗

PubMed1975

7alpha-Carboalkoxy steroidal spirolactones as aldosterone antagonists.

A variety of esters of 17-hydroxy-3-oxo-17alpha-pregn-4-ene-7alpha,21-dicarboxylic acid-gamma-lactone (7a) was synthetized in a sequence using the corresponding 3-oxo-4,6-diene (2) as starting material. The methyl (5), ethyl (7c), and isopropyl (7e) esters as well as the C-1 unsaturated methyl ester (8a) showed good oral and subcutaneous activity (MED less than or equal to 0.41 mg). Some general observations on structure-activity relationships are made.

Administration, Oral↗

PubMed1975

Potassium prorenoate: a new steroidal aldosterone antagonist.

Potassium prorenoate (SC-23992) is a water-soluble steroidal compound with the ability to antagonize the sodium-retaining and, when apparent, the potassium-dissipating effects of mineralocorticoids. A significant natriuretic response was obtained at dosages of 1 mg/kg and approximately 1.8 mg/kg in the dog and rat, respectively. Based upon an elevation in the previously depressed urinary log Na/K ratio, prorenoate possesses an oral potency of 4.6 and 8.1 times that of spironolactone (S), respectively, in the aldosterone and deoxycorticosterone acetate-treated adrenalectomized rat. In the aldosterone-treated dog, the compound had 3.0 times the potency of S and 2.2 times that of a related steroid, potassium canrenoate (SC-14266). Prorenoate and S are relatively inactive at the renal level in adrenalectomized rats without mineralocorticoid replacement. Prorenoate possesses no more than 2% of the natriuretic activity of hydrochlorothiazide in the intact animal. Clearance studies in dogs indicate a direct renal tubular site of interaction between prorenoate and aldosterone independent of changes in renal hemodynamics. The natriuretic response occurred within 100 minutes after a single oral dose and was sustained for at least 7 hours. Prorenoate possesses the pharmacological characteristics of an aldosterone antagonist, in common with those of S.

Adrenal Glands↗

PubMed1974