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Biomedical subjects

C M Kaye

Publications and source records attributed to C M Kaye.

At least 37 records · Page 2Linked to original sources
PubMed1982

The penetration of metronidazole into synovial fluid.

Six patients with non-infected synovial effusions, associated either with inflammatory or degenerative arthropathy and requiring diagnostic or therapeutic aspiration, were given a short course of 400 mg metronidazole (Flagyl) 8-hourly for 3 doses. Serum and synovial fluid (SF) were sampled frequently during this time, and assayed for metronidazole by a specific high pressure liquid-chromatographic method. It was found that concentrations of metronidazole in SF reached those in serum after a short time-lag, and thereafter approximated to the serum concentration. With this regimen, metronidazole concentrations were readily achieved in synovial fluid, above the minimum inhibitory concentrations for most susceptible anaerobes. These results indicate that the drug freely enters the synovial fluid and suggests that metronidazole would prove effective in the treatment of septic arthritis due to anaerobic bacteria.

Administration, Oral↗
PubMed1982

Pharmacokinetics of metronidazole and its principal metabolites and their activity against Gardnerella vaginalis.

The hydroxy metabolite of metronidazole was found to be more active against 21 strains of Gardnerella vaginalis than the parent compound and less affected by culture in carbon dioxide. After 400 mg oral metronidazole (Flagyl) plasma concentrations of the two agents were below the minimum inhibitory concentrations (MICs) for most G vaginalis strains tested. With 2 g metronidazole the plasma concentrations exceeded the MICs of the more sensitive strains. Even with the lower dose of metronidazole clinically useful concentration of metronidazole and its hydroxy metabolite were present in the urine. Urinary excretion of these compounds may contribute to the efficacy of metronidazole in the treatment of vaginitis associated with G vaginalis.

Blood Bactericidal Activity↗
PubMed1981

Observations on the clinical pharmacology and plasma concentrations of diacetolol, the major human metabolite of acebutolol.

1 The pharmacological effects and plasma levels of diacetolol, the major human metabolite of acebutolol, were measured in a double-blind, balanced study in which five healthy men received single oral doses of diacetolol 100, 200, 400 and 800 mg, or placebo, at weekly intervals. 2 Resting and exercise heart rate (HR), forced expiratory volume in 1 second (FEV1), resting and exercise peak expiratory flow rate (PEFR), and plasma concentrations of diacetolol were determined at 0, 2, 4, 6, 8 and 24 h after each treatment. 3 Diacetolol caused a slight dose-related reduction in resting HR and a substantial dose-related reduction in exercise HR. AT the same time it was found that diacetolol had no significant effects on FEV1 and resting and exercise PEFR. 4 Mean highest observed plasma concentrations (ng/ml) of diacetolol were 177 at a mean of 4.4 h after the 100 mg dose, 243 at 4.0 h after the 200 mg dose, 807 at 5.2 h after the 400 mg dose, and 1,306 at 4.4 h after the 800 mg dose. 5 Using the mean data, there was a strong correlation (r = 0.90) between % reduction in exercise HR and the logarithm of the plasma concentration of diacetolol. 6 Diacetolol exhibits marked cardiac beta-adrenoceptor blocking activity in man which is still evident 24 h after the administration of the higher doses of the drug. No adverse effects on pulmonary function could be detected.

Acebutolol↗
PubMed1981

Serum, saliva, and sputum levels of metronidazole in acute exacerbations of chronic bronchitis.

We have evaluated the absorption and the penetration of metronidazole into the bronchial secretions and saliva in acute infective exacerbations of chronic bronchitis. Seventeen patients were given 400 mg orally three times daily for seven days and "steady state" levels were measured in serum, saliva, and sputum on the last day of treatment. Mean levels in the three biological fluids were not significantly different. Higher metronidazole levels in sputum tended to occur in patients with higher serum levels. In all but one patient, levels in serum and saliva were well within the therapeutic range. We conclude that this oral regimen results in therapeutic tissue levels in acute exacerbations of chronic bronchitis.

Absorption↗
PubMed1978

Studies of cardioselectivity and partial agonist activity in beta-adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercise.

1 The effects of beta-adrenoceptor antagonists given in single doses by oral or intravenous routes were examined in two double-blind controlled studies performed in healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardized exercise. 2 Propranolol 80 mg and metoprolol 100 mg orally tended to reduce, and propranolol and metoprolol 0.2 mg/kg intravenously did reduce the physiological increase in PEFR during exercise; oxprenolol 80 mg orally and 0.2 mg/kg intravenously did not. Practolol 200 mg orally reduced this increase, but practolol 1 mg/kg intravenously did not. 3 In a third study of similar design, pindolol 0.05 mg/kg intravenously did not affect exercise-induced increase in PEFR. 4 Heart rate during exercise was reduced to a comparable extent at different times by all the active treatments. 5 Oxprenolol and pindolol share with practolol the property of partial agonist activity, which might contribute to their apparent lack of effect on airways resistance. A further possibility is that alpha-adrenoceptor blockade helps to maintain exercise-induced increase in PEFR.

Adrenergic beta-Antagonists↗
PubMed1977

An investigation of "absolute plasma level effect relationships" and "absolute cardioselectivity" with respect to beta-adrenoceptor blockade.

In a group of 6 healthy (but physically unfit) volunteers an investigation was made of whether there was a true plasma level effect relationship and absolute "cardioselectivity" with respect to beta-adrenoceptor blockade due to practolol. To this end three treatments were given orally, namely placebo, practolol 100 mg and practolol 400 mg. Cardiac beta-adrenoceptor blockade was assessed by measuring the inhibition of exercise heart rate and pulmonary beta-adrenoceptor blockade was assessed by measuring the reduction in exercise peak flow rate, up to 24 h after each dose. Plasma practolol levels were determined spectrophotometrically. From the results obtained there was no reason to doubt the existence of a valid relationship between cardiac beta-adrenoceptor blocking activity and the plasma concentration of practolol. It was also concluded that even in non-asthmatics, practolol does not possess absolute "cardioselectivity" since significant reductions in peak flow rate were discernible during vigorous exercise, particularly when the large dose had been given.

Adult↗
PubMed1977

Pharmacokinetics of salicylate and indomethacin in coeliac disease.

The plasma concentrations of salicylate and indomethacin were measured after a single oral dose of aspirin (600 mg) and indomethacin (50 mg) in twelve starved normal subjects and twelve adult patients with coeliac disease. The absorption of salicylate in the coeliac patients was faster than in the normal subjects. The plasma concentration/time curve of indomethacin in both groups was similar during the absorption phase, but there were significant differences between the groups in its elimination. The abnormal absorption pattern of salicylate in coeliac disease does not appear to be related to its pKa. Possible causes of the difference in salicylate absorption include changes in gastric emptying or altered small intestinal permeability.

Adult↗
PubMed1977

The different effects of sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin in man.

The influence of oral sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin has been studied in normal volunteers. While sodium bicarbonate appeared to increase indomethacin absorption, aluminium hydroxide markedly reduced both the rate and extent of absorption. The buccal absorption of indomethacin over the pH range 5-9 was also studied in normal volunteers, and showed that the percentage absorption increased markedly as the pH was reduced. The clinical importance both of pH-partition and of adsorption are discussed in the context of antacid interactions. It is concluded that caution must be exercised when prescribing an antacid with other orally-administered drugs.

Absorption↗
PubMed1976

Observations on the pharmacokinetics of acebutolol.

Using a balance, randomized, crossover design, single intravenous (1 mg/kg) or oral (3 X 100 mg) doses of acebutolol were administered at weekly intervals to 6 healthy volunteers. For each subject venous blood samples and timed urine collections were obtained after each treatment. Plasma and urinary acebutolol levels were measured by a spectrophotometric method that measures acebutolol and its N-acetyl metabolite (which has equivalent cardiac activity). Using a computer program, various pharmacokinetic parameters were estimated from the date of each subject. From the intravenous data (obtained up to 6 hr after dosing), the following mean (+/-SD) values were found: distribution half-life (T 1/2D), 0.60 (+/-0.43) hr, plasma elimination half-life (T 1/2El), 3.2 (+/-1.1) hr, apparent volume of distribution (VD), 224 (+/-69) L, and apparent VD/kg, 3.0 (+/-0.8) L/kg. Using the oral data (obtained up to 10 hr after dosing), the value for T 1/2El was 3.2 (+/-0.9) hr. The mean cumulative urinary recovery (expressed as % dose) after the intravenous route was about 60%, while that after the oral route was of the order of 35%, suggesting that about half of the oral dose reached the systemic circulation. The mean creatinine clearance of the 6 subjects was 103 (+/-7) ml/min, while the value (obtained between 2 and 4 hr after intravenous dosing) for renal clearance of acebutolol as measured was 298 (+/-68) ml/min and the corresponding plasma clearance was 818 (+/-64) ml/min. These results support the occurrence of substantial nonrenal elimination and renal tubular secretion.

Acebutolol↗