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Biomedical subjects

P Collste

Publications and source records attributed to P Collste.

31 records · Page 2Linked to original sources
PubMed1976

Interindividual differences in chlorthalidone concentration in plasma and red cells of man after single and multiple doses.

A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorathidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n = 10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those preducted from the single oral dose studies in healthy volunteers.

Adult↗
PubMed1976

Plasma levels and effects of metoprolol on blood pressure, adrenergic beta receptor blockade, and plasma renin activity in essential hypertension.

The effects of metoprolol, a selective beta adrenergic receptor antagonist, on blood pressure, beta receptor blockade (antagoinst of isoproterenol and exercise tachycardia), and plasma renin activity (PRA) have been compared with those of placebo in 16 patients with essential hypertension. The dose of metroprolol was 25 mg three times daily for 1 wk and thereafter 100 mg three times daily for 5 wk. The mean decrease in blood pressure during treatment with metoprolol was 24 +/- 3.8 (SEM)/10 +/- 2.1 mm Hg in the lying position and 23 +/- 4.4/9 +/- 3.1 mm Hg after 1 min in the standing position. At a dose of 2.9 to 5.4 mg/kg, steady-state plasma concentrations of metoprolol varied 17-fold (from 20 to 341 ng/ml) between patients and correlated with the interindividual variability in isoproterenol antagonism (r = 0.58, p less than 0.05) and decrease in exercise tachycardia (r = 0.65, p less than 0.01). By contrast, neither of these variables correlated with the dose of metoprolol in mg/kg. Metoprolol decreased PRA by 67 +/- 1.9 and 71 +/- 1.2% in the lying and standing positions, respectively. The decrease in the mean arterial blood pressure in the lying position was significantly correlated to the PRA during the placebo period (r = 0.61, p less than 0.05) but not to the plasma steady-state levels of metoprolol, the degree of beta receptor blockade, and the decrease in PRA.

Adrenergic beta-Antagonists↗
PubMed1975

Distribution and elimination kinetics of carbamazepine in man.

Carbamazepine (2.7-3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1-7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 1/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2-3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.

Administration, Oral↗
PubMed1975

Acetylation of procaine amide in man. A preliminary communication.

The metabolism of procaine amide was studied in 41 cardiac patients who had achieved steady state plasma concentrations of the drug. Acetylated procaine amide accounted for 31 +/- 12% (range 16-63%) of the overall urinary recovery of the drug and is therefore a main metabolite in man. Plasma levels of the metabolite were usually lower but sometimes exceeded those of the parent compound with variations between 1 and 15 mug/ml. The metabolite had a weaker effect than procaine amide on the maximal electrical driving velocity of isolated atrial strips from guinea pig.

Acetylation↗