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L Vereczkey

Publications and source records attributed to L Vereczkey.

At least 55 records · Page 3Linked to original sources
PubMed1987

Pharmacokinetic studies of [14C]-flumecinol in humans.

The pharmacokinetics of 14C-labelled 3-trifluoro-methyl-alpha-ethylbenzhydrol (flumecinol, RGH-3332, Zixoryn), a hepatic enzyme inducer, has been studied in 6 male healthy volunteers after a single oral dose of 100 mg (11.1 Mbq; 300 microCi). Flumecinol concentration in plasma was determined (0-96 h) by capillary gas-liquid chromatography. Total radioactivity was assayed by liquid scintillation counting. The peak concentration of unchanged flumecinol in the plasma (130.2 +/- 37.7 ng/ml S.D.) was detected 2.1 h after dosing. The maximum total radioactivity concentration (1414.4 +/- 158.9 ng eq./ml) was found at 2.3 h. The ratio of the plasma radioactivity level to unchanged flumecinol indicated a rapid metabolic transformation and a marked first-pass effect in man. A two-compartment open model was constructed to describe the pharmacokinetics of the drug. The unchanged drug was eliminated from plasma with a biological half-life of 20.7 +/- 1.8 h giving a total body clearance value of 100.9 +/- 33.8 l/h. The volume of distribution of flumecinol was found to be 41.4 +/- 18.4 l/kg. However, the biological half-life of total radioactivity was much longer (35.2 +/- 11.9 h) than that of the decrease of unchanged drug. The value of total body clearance (4.1 +/- 0.6 l/h) and volume of distribution (3.2 +/- 1.6 l/kg) were found to be much lower than that of unchanged flumecinol. Radioactivity excreted with urine was 78.8 +/- 5.9% and with faeces 12.0 +/- 5.3% during 120 h.

Adult↗
PubMed1987

Comparative bioavailability study of two preparations of alpha-methyldopa after single, oral doses.

Bioavailability of alpha-methyldopa from a film coated tablet Dopegyt (EGIS Pharmaceutical Works, Budapest, Hungary) and from Aldometil (MSD, Sharp and Dohme GmbH, Munich, FRG) containing 250 mg of effective substance, was investigated in a crossover study in six patients with mild hypertension having normal renal and liver functions. Alpha-methyldopa was determined in plasma by fluorometry. There was no difference in the pharmacokinetic parameters calculated (Cl, Vd, AUC, t1/2) indicating that the two preparations are bioequivalent.

Adult↗
PubMed1986

Studies on the pharmacokinetics and metabolism of N(4)-carbamoyl-1,3,4,5-dihydro-diazepam (Uxepam(R)) in rats, dogs and man.

The pharmacokinetics and metabolism of Uxepam(R), a new minor tranquillizer, have been investigated in rats [2], dogs and man. For the experiments in rats [2] separation of metabolites of 2-(14)C-uxepam was achieved by thin-layer chromatography. In the experiments on dogs and man, Extrelut microcolumns were used for preseparation. Recovery was 95% +/- 12.77 (S.D.) determined by radioactive tracer experiments. The compounds were separated and determined by reversed-phase HPLC with UV detection at 240 nm. The limit of detection for uxepam was 10 ng ml(-1). The metabolises were identified by mass spectrometry. The main metabolites in the rat were desmethyl-uxepam, 5-hydroxy-phenyl-desmethyl-uxepam and diazepam. Desmethyl-carbamoyl-dihydro-diazepam, diazepam and desmethyl-diazepam were found in human plasma. In dogs only one metabolite, desmethyl-uxepam, was detected in plasma. Enterohepatic recycling was observed in dogs and in humans.

Journal Article↗
PubMed1985

Pharmacokinetics of vinpocetine and its metabolite, apovincaminic acid, in plasma and cerebrospinal fluid after intravenous infusion.

The pharmacokinetics of vinpocetine (ethyl apovincaminate, Cavinton) and its metabolite, apovincaminic acid, was studied in patients with cerebrovascular disorders. Vinpocetine (1 mg/kg) was infused intravenously over 25 min. The elimination half-life of the parent drug in plasma was 4.7+/-2.13 h. Total clearance of vinpocetine was 0.79+/-0.1 1 h(-1) kg(-1). The presence of vinpocetine in cerebrospinal fluid shows that the drug is able to pass through the blood-brain barrier and reach the central nervous system which is a possible site of action. The maximum increase of cerebral blood flow (25%) was measured at 32 min after the start of the infusion.

Journal Article↗
PubMed1982

Determination of apovincaminic acid in human plasma by gas-liquid chromatography.

High-resolution capillary gas-liquid chromatography (GLC) and highly sensitive and selective nitrogen-phosphorus flame ionization detection were applied for the detection of apovincaminic acid (AVA), the main metabolite of the cerebral vasodilator vinpocetine in human plasma. AVA was recovered from plasma by ion-pair extraction and determined by GLC as its methyl ester after derivation with diazomethane. An acid-base washing technique was used in order to reduce the contamination of GLC samples by material of endogenous origin to a minimum. The lowest detection limit of the method is 2 ng of AVA per ml of plasma.

Cerebrovascular Disorders↗
PubMed1982

Determination of apovincaminic acid in biological samples by high-performance liquid chromatography.

A method is described for measuring the concentrations of apovincaminic acid and vincaminic acid (internal standard) in blood plasma and urine by high-performance liquid chromatography using ion pair extraction. The main metabolite of vinpocetine, apovincaminic acid, and vincaminic acid were extracted from 1 ml of plasma and urine into chloroform as an ion pair using tetrabutylammonium hydroxide as counter ion. Analysis was carried out on a reversed-phase column of RP-8 with acetonitrile-0.0075 M phosphate buffer (28:72) at pH 3.5 as mobile phase. The eluted derivatives were detected by UV absorption at 254 nm. The sensitivity of the method is 20 ng/ml for AVA in plasma and urine samples. The relative recovery of these compounds added to plasma was about 50%.

Chromatography, High Pressure Liquid↗
PubMed1982

Pharmacokinetic studies of flumecinol in man and dog.

The pharmacokinetics of flumecinol (Zixoryn) a new hepatic enzyme inducer has been studied in four beagle dogs and six healthy volunteers. The beagle dogs and the volunteers received the drug orally in a dose of 40 mg/kg of body weight and of 100 mg single dose respectively. Flumecinol was extracted from plasma with diethyl ether and analysed by gas-liquid chromatography using a flame ionisation detector (FID). The pharmacokinetic parameters of flumecinol were determined by computer evaluation of the plasma concentration-time curves. The peak plasma concentrations were found to be 5.3 and 2.1 hours in dogs and humans, respectively. Flumecinol is eliminated from the plasma of dogs and humans with half-lives of 38.95 and 17.16 hours, corresponding to a clearance of 53.2 litres/hour and 94.0 litres/hour, respectively.

Adult↗
PubMed1981

Pharmacokinetics of pipecurium bromide, a new non-depolarizing neuromuscular blocking agent, in humans.

The pharmacokinetics of 2 beta, 16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha, 17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, Arduan), a new non-depolarizing neuromuscular blocking agent, was studied in surgical patients. Plasma concentration-time curves of pipecurium bromide were evaluated by fitting the data to a bi-exponential equation. The average half-lives were T 1/2 alpha = 4.1 +/- 1.4 (n = 8) and T 1/2 beta = 44 +/- 7 (n = 8) min. The pharmacokinetic parameters of pipecurium bromide were found as follows: apparent distribution volume V beta = 261 +/- 28 (n = 8) ml/kg, plasma clearance Cl = 320 +/- 55 (n = 8) ml/min. The microconstants of two-compartment open models were also calculated.

Adult↗
PubMed1980

Disposition of pipecurium bromide in rats.

The disposition of 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), a new neuromuscular blocking agent, was studied in rats by using labelled substance. Radioactive substance is rapidly taken up by the liver and to a lesser extent by the kidneys. The compound is retained by the liver for a longer period of time, some 6% of the administered 14C-activity can be recovered from the liver 21 days after the i.v. administration of the drug. Only traces of radioactivity could be detected in the brain and less than 0.1% of the dose could be found in the foetus. Binding to rat plasma protein is of about 30%. The compound seems to be eliminated with urine, the excreted amount being 37.55 +/- 11.91% and 45.44 +/- 17.29% during 24 and 48 h, respectively. No radioactivity was detected in the expired air.

Androstane-3,17-diol↗
PubMed1980

Metabolism of vincamine in the rat in vivo and in vitro.

Metabolism of vincamine has been studied in rats in vivo and in vitro using tritium labelled vincamine. Radioactivity was excreted with urine and faeces in an amount of about 62% during 72 h after i.v., i.p. and p.o. administration of the drug. From bile about 40% radioactivity could be recovered during 6 h following i.p. administration. Vincamine is excreted in unchanged form in an amount of 4-6%. In an in vitro system containing rat liver homogenate 6 alpha- and 6 beta-hydroxy-vincamine are formed, as their structures could be deduced from the mass spectrometric data. Rat plasma probably hydrolizes vincamine to vincaminic acid, but the presence of vincaminic acid could not be demonstrated, neither in urine nor in bile. Mass spectrometric investigations of the urinary and biliary metabolites have shown that beyond 6 alpha- and 6 beta-hydroxy-vincamine, their further oxidized form, 6-keto-vincamine also appears. 6 alpha-, 6 beta-hydroxy-vincamine, 6-keto-vincamine and vincamine are eliminated with urine and bile in part as conjugates. Among the metabolites (+)-eburnamonine (vincamone) was also found, which is supposed to be the degradation product of vincaminic acid. The identified compounds are responsible for about 70% of urinary and 30% of biliary radioactivities.

Animals↗