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Biomedical subjects

C M Kaye

Publications and source records attributed to C M Kaye.

At least 55 records · Page 3Linked to original sources
PubMed1976

Absorption of propranolol and practolol in Coeliac disease.

Plasma concentrations of propranolol and practolol were measured in patients with coeliac disease and normal subjects. The mean plasma propranolol concentration in the coeliac patients was higher throughout the period of study, the differences being significant at one, six, and eight hours. The plasma concentration profile of practolol in the coeliacs followed a similar pattern but lagged behind that of the normal subjects. A possible reason for these differences is an alteration in the rate of drug diffusion across the atrophic mucosa of the upper jejunum in coeliac disease. Analysis of the results of the propranolol study suggests that an increase in the rate of absorption combined with saturation of first pass extraction may account for the increased plasma concentrations of unchanged propranolol found in coeliac disease. These abnormalities of drug absorption do not appear to be related to the duration of treatment with a gluten free diet.

Adult↗
PubMed1975

Cardiac and pulmonary effects of acebutolol.

In a double-blind randomised study, single intravenous doses of propranolol (0-1 mg. per kg.), practolol (1 mg. per kg.), acebutolol (1 mg. per kg.), or placebo were each administered at weekly intervals to six healthy volunteers. Forced expiratory volume in 1 second (F.E.V.1), resting and exercise heart-rate, and resting and exercise peak flow-rate (P.F.R.) were determined before and at 2, 3, 4, and 6 hours after each treatment. Venous blood-samples were also obtained at these times. Compared with placebo, resting heart-rate was reduced after all three drugs, but the corresponding differences in exercise heart-rate were much greater, more consistent, and of greater statistical significance. At 2, 3, and 4 hours when acebutolol and propranolol produced equivalent cardiac beta-blocking activity (judged by reductions in exercise heart-rate), their mean plasma concentratios were in the ratio of about 8/1; and at 2 hours when practolol and acebutolol gave rise to almost equivalent cardiac beta blockade, their mean plasma concentratio ration was 3/1. At times, reductions in F.E.V.1 and resting P.F.R. after propranolol (but not after practolol or acebutolol) were significantly greater than the corresponding changes after placebo. The reductions in exercies P.F.R. after propranolol (6 hours) and acebutolol (4 hours) (but not after practolol) were significantly greater than the changes after placebo. Changes in F.E.V.1, resting and exercise P.F.R. after propranolol, and the corresponding changes after practolol, were significantly different, all of which confirmed that practolol was more cardioselective than propranolo. In general, the reductions in F.E.V.1 and resting P.F.R. after acebutolol were slightly smaller than after propranolol, excepting at 6 hours when the difference between them was significant. The reductions in exercise P;F.R. after acebutolol and propranolol were of the same order, there being no significant differences between the two, whereas the reductions after acebutolol were clearly greater than the corresponding changes after practolol, the differences being significant at 2, 3, and 4 hours.

Acebutolol↗
PubMed1975

Procainamide absorption studies to test the feasibility of using a sustained-release preparation.

Using in vitro techniques it was confirmed that whilst the release of procainamide from the conventional formulation (Pronestyl) was rapid, that from the sustained-release preparation (Cardiorytmin Retard) occurred over a prolonged period. 2 The peak plasma procainamide concentrations after single doses of Cardiorytmin Retard were relatively lower and occurred later than those after single doses of Pronestyl. Furthermore, after reaching a peak, the fall in plasma procainamide concentration was less rapid after the sustained-release preparation. Early urinary recovery of procainamide in patients and in healthy volunteers was greater after Pronestyl than after Cardiorytmin Retard, though overall recovery in urine was similar. These findings indicate that the absorption of the sustained-release preparation is slower, though the overall bioavailabilities of the two preparations are almost the same. 3 These results confirm the feasibility of using a sustained-release procainamide preparation, such as Cardiorytmin Retard, since it would be possible to administer the same amount of drug in fewer daily doses without plasma concentrations becoming ineffective towards the end of each dosing interval.

Adult↗
PubMed1975

An investigation into the cardiac and pulmonary beta-adrenoceptor blocking activity of ICI 66,082 in man.

1 Oral ICI 66,082 (200 mg) or water (control treatment) were each administered to six healthy volunteers. 2 The heart rate (HR) and peak flow rate (PFR) were measured at rest and during vigorous exercise before and at intervals up to 24 h after each treatment. 3 ICI 66,082 produced significant reductions in exercise HR at all times compared with the changes after the control treatment (P less than 0.001), whereas with resting HR, corresponding significant reductions only occurred at 2,3 and 4 h (P less than 0.05). 4 Although there was no change in resting PFR, significant reductions in exercise PFR, compared with the changes after the control treatment, occurred at all times excepting at 2 h after ICI 66,082 (P less than 0.025). 5 The findings are consistent with ICI 66,082 possessing partial cardioselectivity. 6 Plasma levels and renal excretion of the drug were determined. Urinary recovery was variable which, together with the plasma concentration/effect relationships obtained, raise the possibility that ICI 66,082 is metabolized in man.

Adult↗
PubMed1975

The effect of age on plasma levels of propranolol and practolol in man.

1. Plasma levels of propranolol and practolol were measured in groups of elderly and young subjects, after the oral administration of propranolol (40 mg) and practolol (200 mg) on separate occasions. 2. At all sampling times the mean plasma propranolol level in the group of elderly subjects was substantially greater than the corresponding level in the group of young subjects, there being a significant difference between the two, and a fourfold difference in the mean peak levels. 3. After practolol, there was no significant difference between the mean plasma concentrations of the drug in the two groups for the first 2 hours. Subsequently, the mean plasma levels in the group of elderly subjects were somewhat higher than the corresponding levels in the young group, the differences between the two reaching significance. 4. It is suggested that there is a need to substantially reduce the dose of propranolol given to elderly patients. With practolol, however, no reduction is necessary providing renal function is normal for the patient's age.

Administration, Oral↗
PubMed1975

A study of practolol elimination in all grades of chronic renal failure.

Plasma and renal elimination of practolol have been studied in 12 patients with varying degrees of stable chronic renal failure and 14 normal volunteers. Each individual received 200 mg of oral practolol. The mean time to peak plasma level in the group of patients with renal failure was later than in the normal group, the difference between the two being significant. There were significant correlations between plasma practolol clearance and creatinine clearance, and also between renal practolol clearance and creatinine clearance. Total clearance of practolol from plasma was slightly higher than its renal clearance, the difference being significant, which suggested a small non-renal component to elimination. Renal practolol clearances tended to exceed creatinine clearances, the difference being significant, suggesting some renal tubular secretion of the drug. It is suggested that--in patients with chronic renal failure--the maintenance dose of practolol be reduced roughly in proportion to the reduction in creatinine clearance from normal. If effective plasma practolol concentrations are required quickly, the need for giving a loading dose becomes important under such circumstances.

Adult↗
PubMed1974

New approach to assessment of cardioselectivity of beta-blocking drugs.

Propranolol, practolol, and placebo were each given intravenously at weekly intervals to six normal subjects, and their effects on respiratory function tests and heart rates assessed. The reduction in the exercise heart rate after each of the two drugs was most comparable at six hours, indicating a similar degree of cardiac beta-blockade, when the plasma concentration ratio of practolol to propranolol was 28:1. The peak flow rate (PFR) was higher at all times during exercise than at rest. There were significant differences between the changes in resting and exercise PFR after placebo and the reductions after propranolol (except at 24 hours), but not after practolol-and the latter's influence on PFR seemed to be intermediate to that of propranolol and placebo. At six hours, when the cardiac beta-blocking activity of the two drugs was almost the same, there was a significant difference (P 0.025) between the reductions in exercise PFR associated with each drug.

Adult↗
PubMed1973

Biosynthesis of mercapturic acids from allyl alcohol, allyl esters and acrolein.

1. 3-Hydroxypropylmercapturic acid, i.e. N-acetyl-S-(3-hydroxypropyl)-l-cysteine, was isolated, as its dicyclohexylammonium salt, from the urine of rats after the subcutaneous injection of each of the following compounds: allyl alcohol, allyl formate, allyl propionate, allyl nitrate, acrolein and S-(3-hydroxypropyl)-l-cysteine. 2. Allylmercapturic acid, i.e. N-acetyl-S-allyl-l-cysteine, was isolated from the urine of rats after the subcutaneous injection of each of the following compounds: triallyl phosphate, sodium allyl sulphate and allyl nitrate. The sulphoxide of allylmercapturic acid was detected in the urine excreted by these rats. 3. 3-Hydroxypropylmercapturic acid was identified by g.l.c. as a metabolite of allyl acetate, allyl stearate, allyl benzoate, diallyl phthalate, allyl nitrite, triallyl phosphate and sodium allyl sulphate. 4. S-(3-Hydroxypropyl)-l-cysteine was detected in the bile of a rat dosed with allyl acetate.

Acetylcysteine↗