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Biomedical subjects

R Gugler

Publications and source records attributed to R Gugler.

At least 109 records · Page 6Linked to original sources
PubMed1979

Malignant pheochromocytoma. Effect of oral alpha-methyl-p-tyrosine upon catecholamine metabolism.

In a patient with malignant pheochromocytoma treated unsuccessfully with propranolol and phenoxybenzamine the additional therapy with alpha-methyl-p-tyrosine resulted in a substantial decrease of the blood pressure to almost normal values. His general condition improved considerably. During therapy the urinary excretion rates of catecholamines and all their metabolites dropped to about 50% of control values. O-Hydroxylation of alpha-methyl-p-tyrosine could be demonstrated by the isolation of alpha-methyldopa and alpha-methylnormetanephrine. After discontinuation of treatment with alpha-methyl-p-tyrosine blood pressure and catecholamines returned to control values within two days.

Administration, Oral↗
PubMed1978

Single and multiple dose pharmacokinetics of pindolol.

The pharmacokinetics of pindolol were studied in six healthy individuals following a single 10 mg dose (SD) and multiple (5 mg tid over 6 days) dose (MD). The plasma elimination half-life was identical after SD (4.7 +/- 0,8h) and MD (4.1 +/- 1.1h). Steady state plasma concentrations were reached after 36 h and remained stable thereafter. The variation in steady state concentrations was small in each individual and also between individuals. The steady state concentration of pindolol can be predicted from the pharmacokinetic data obtained after a single dose. The results of the present study suggest that the disposition of pindolol is linear over the concentration range studied.

Adult↗
PubMed1978

Clofibrate kinetics after single and multiple doses.

The kinetics of chlorphenoxyisobutyric acid (CPIB) were studied in 5 healthy subjects after single 500-mg, 1,000-mg, and 2,000-mg doses of clofibrate, and in steady-state after 8 days' treatment with 1,000 mg twice daily. Maximum plasma concentrations of CPIB were observed 4 to 6 hr after dosing. A mean plasma half-life of 16.7 hr was recorded which was independent of dose and duration of treatment. Total plasma clearance (-Cl) calculated from area under the curve with the use of the total plasma concentration was 5.6 ml/min for the 500-and the 1,000-mg doses but increased to 6.8 ml/min for the 2,000-mg dose and was even higher (8.1 ml/min) in steady-state. This change in -Cl is a consequence of progressive reduction in the plasma protein binding of clofibrate at plasma concentrations above 50 microgram/ml, since -Cl rises in association with reduced protein binding at the high plasma concentrations measured after the 2,000-mg single dose and in steady-state. -Cl and apparent volume of distribution were identical for all doses tested when calculations were based on the nonprotein-bound CPIB concentrations only. Due to the inconsistant protein binding of CPIB, total steady-state concentrations could not be predicted from the single dose kinetic data.

Adult↗
PubMed1978

Plasma protein binding of valproic acid in healthy subjects and in patients with renal disease.

1 Based on the Scatchard plot of the binding data of valproic acid (VPA) it is concluded that the drug is bound by two groups of binding sites with the association constants K1=40.0 X 10(-3) and K2=0.39 X 10(3), and the number of binding sites n1=1.5 and n2=6.8. 2 The binding is dependent on dialysis time, on temperature, on the drug concentration, and on the protein concentration in plasma. 3 At therapeutic plasma concentrations unbound VPA is 8.4 +/- 2.5%, but is increased to 20.3 +/- 4.7% in patients with significant impairment of renal function (P less than 0.001). 4 In patients with renal disease a good correlation is found between unbound VPA and serum creatinine, creatinine clearance, blood nitrogen and uric acid, respectively. A poor correlation is seen between unbound VPA and total protein or albumin concentration in plasma.

Binding Sites↗
PubMed1978

[Valproic acid in the treatment of epilepsy with special emphasis on serum level determination (author's transl)].

Valproic acid has become a regular component of antiepileptic therapy. Generally it is used against genetically caused, primary generalized epilepsies with bilateral hypersynchronous neuronal discharges in the EEG. An improvement can also be observed by Valproic acid-treatment for secondary generalized and partial epilepsies. Therapeutic results could possibly be improved through a consideration of the serum concentration of valproic acid. Some of the commercial preparations contain the sodium salt of Valproic acid. The free acid which is quickly absorbed, is released in the stomach (tablet) or in the intestine (dragee). The half life is about 15 to 17 hours (one finds a range of 6 to 20 hours in the literature). In view of the half life, it is recommended that the daily dose should be divided into three single doses. About 84 to 95% of the substance is protein bound. Up to now, clinically relevant observations concerning the displacement of valproic acid from its protein binding are unknown. Recently in in vitro studies a decreased protein binding of valproic acid due to phenylbutazone, salicylic acid, and sulfadimethoxine and vice versa, a displacement of phenobarbital and phenytoin caused by valproic acid could be demonstrated. The therapeutic range of the serum level was between 50 and 120 mcg/ml. Individual patients showed that the dispensed dose did not reliably yield the expected serum levels. The necessary daily dose lies for adults between 600 and 2400 mg, in children between 15 and 150 mg/kg. The wide range of allowable dosis is dependent on whether or not valproic acid is to be given in conjunction with other antiepileptic drugs. When phenobarbital and valproic acid are given in conjunction one should be alert for a rise in the phenobarbital serum level. Results of studies in which valproic acid was combined with several other antiepileptic and psychotropic drugs are reported. The majority of the researchers determine a clear parallelism between clinical improvement and a normalization of the EEG in primary generalized epilepsies with bilateral synchronous 3/sec. spikes and waves. The background activity, determined by visual inspection, is not affected. Few workers discuss the correlation of the side effects of valproic acid and its serum level. Tiredness and impaired function of thrombocytes has been observed to be dependent on the valproic acid plasma level.

Blood Platelets↗
PubMed1978

[Gastroscopy and rinsing of the gastric wall under sight in drug intoxication (author's transl)].

Gastric rinsing during gastroscopy is presented as a new, effective, uncomplicated method of primary elimination of poison, as a part of a new diagnostic and therapeutic concept for patients intoxicated with hypnotics. The advantage of this active therapy is a fast elimination of the toxic substance and prevention of secondary complications. The diagnostic value of gastroscopy and radiological examination in patients with unexplained comatous states is emphasized.

Coma↗
PubMed1977

Disposition of valproic acid in man.

The pharmacokinetics of valproic acid (VPA) have been studied in 6 healthy subjects following a single 600 mg dose, and after multiple doses over 12 days (1200 mg daily) of enteric-coated sodium valproate. A time lag before absorption of 1 to 2 h was observed in each subject, and then absorption was rapid, peak concentrations being recorded 3 to 4 h after administration of the dose. The plasma level decline was biphasic with a terminal half-life of 15.9 +/- 2.6 h in the single dose and 17.3 +/- 3.0 h in the multiple dose experiments. There was no evidence of dose dependent kinetics or autoinduction. Total plasma clearance was 0.0064 +/- 0.0011 l/kg X h. The apparent volume of distribution was small at 0.15 +/- 0.2 l/kg. The mean steady state plasma concentration (Css) reached after 4 days was 81.3 +/- 13.0 microgram/ml. Css observed was lower than Css predicted (99.2 +/- 14.7 microgram/ml) from single dose kinetics (p less than 0.001). The difference was probably due to a reduction in plasma protein binding at higher concentrations. VPA concentration in saliva was between 0.4 and 4.5% of the total plasma concentration and was not equal to the concentration of unbound drug in plasma (6.7 +/- 0.8% unbound). 3.2% of the dose was excreted in urine as the parent drug and 21.2% as conjugated metabolites.

Adult↗