Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers.

The effect of a high-fat meal on the oral bioavailability of deramciclane 30 mg tablet was evaluated in 18 healthy male volunteers in a randomised, single dose, two-way crossover study. The drug was administered following an overnight fast or a standardised high-fat breakfast. The plasma concentrations of deramciclane and N-desmethylderamciclane were determined by using a validated HPLC-MS -MS/MS method.

Comparative bioavailability of alpha-methyldopa normal and film tablet formulations after single oral administration in healthy volunteers.

In a single dose, randomized, cross-over study, with one week of wash-out period, the relative bioavailability of Dopegyt tablets containing 250 mg alpha-methyldopa (AMD) and Presinol film tablets with identical active ingredient content was examined in 24 healthy volunteers. Since technologically two completely different preparations (a film-tablet and a non-film-tablet) having significantly different in vitro dissolution were to be compared, both preparations were compared to a third one, AMD solution (Dopegyt solution) with 250 mg/50 ml concentration. Plasma concentrations of the drug were measured for 24 hours post-dose, applying HPLC with fluorometric detection.

[Role of food interaction pharmacokinetic studies in drug development. Food interaction studies of theophylline and nifedipine retard and buspirone tablets].

Due to several mechanism, meals may modify the pharmacokinetics of drug products, thereby eliciting to clinically significant food interaction. Food interactions with the drug substance and with the drug formulation should be distinguished. Food interaction of different drug products containing the same active ingredient can be various depending on the pharmaceutical formulation technology.

Validated liquid chromatographic method for the determination of N-3-(2,2,5,5-tetramethyl-3-pirrolin-3-carboxamidopropylphthalimide hydrochloride), a novel antiarrhythmic agent in human plasma.

A simple high-performance liquid chromatographic method with ultraviolet absorbance detection has been developed to determine the concentration of N-3-(2,2,5,5-tetramethyl-3-pirrolin-3-carboxamidopropylphthalim ide hydrochloride; A-2545), a new antiarrhythmic agent from human plasma. Separation of the investigated compound and internal standard was achieved on a Nucleosil 7 C18 column with a 0.01-M potassium dihydrogenphosphate buffer (pH 2.

High-performance liquid chromatographic method with coulometric detection for the determination of buspirone in human plasma by means of a column-switching technique.

A reversed-phase high-performance liquid chromatographic method with electrochemical detection has been developed for the determination of buspirone from human plasma. The separation was carried out by using a Supelcosil ABZ+ plus C18 reversed-phase column and 0.05 M potassium dihydrogenphosphate (pH 6.

Liquid chromatographic method for the determination of ticlopidine in human plasma.

A simple high-performance liquid chromatographic method for determination of ticlopidine in human plasma using ultra violet detection was developed. The separation of the investigated compound and internal standard was achieved on a C18 BD column with a 0.01 M potassium dihydrogen phosphate buffer (pH 4)-acetonitrile-methanol (20:40:40, v/v) mobile phase.

[Human pharmacokinetic study of nerisopam and its n-acetyl metabolite].

It was established during the human phase I study of nerisopam, a new anxiolytic drug, that nerisopam (EGIS-6775) shows two, while N-acetyl metabolite (EGIS-7649) shows one compartmental pharmacokinetic behaviour. Acetylation of nerisopam is polymorph, so that volunteers belonging into slow or fast acetylating group show significantly different plasma concentration. Observed pharmacokinetic differences are primarily manifested in the absorption phase, and not in the elimination one.

[Pharmacokinetic study of nerisopam and its n-acetyl metabolite in rats].

Three doses were administered to the rats during the pharmacokinetic study of nerisopam and the plasma concentrations of nerisopam and its N-acetyl metabolite were determined parallelly by means of validated SPE-HPLC method developed by the authors. The pharmacokinetics of nerisopam could be described by a two-compartment open model in rats, it was absorbed rapidly and could be measured in plasma for about 8 hours. The peak plasma concentration of the N-acetyl metabolite was reached rapidly a little bit later than that of the parent compound, similarly to the human plasma, and it could be measured for about 12 hours.

[Validity of a liquid chromatographic (HPLC) method for the determination of ticlopidine in human plasma].

A simple high-performance liquid chromatographic method for determination of ticlopidine in human plasma using UV detection was developed. The separation of the investigated compound and internal standard was achieved on "BST Rutin" 10, C18 BD column with a 0.01 M, (pH 4) potassium dihydrogen phosphate bufferacetonitrile-methanol (20:40:40 v/v) mobile phase.

Determination of alpha-methyldopa in human plasma by validated high-performance liquid chromatography with fluorescence detection.

A sensitive reversed-phase gradient elution high-performance liquid chromatographic method with fluorescence detection has been developed for the determination of alpha-methyldopa (AMD) in human plasma. Separation of the investigated compound and the 3,4-dihydroxyphenylalanine (DOPA) internal standard was achieved on a Nucleosil 7 C18 column with a 5 mM heptanesulphonic acid sodium salt containing 0.05 M potassium dihydrogenphosphate (pH 3.

Simultaneous determination of nerisopam, a novel anxiolytic agent showing polymorphic metabolism, and its N-acetyl metabolite from human plasma by a validated high performance liquid chromatographic method.

A sensitive reversed-phase high-performance liquid chromatographic method with ultraviolet absorbance detection has been developed to simultaneously determine the concentrations of nerisopam (EGIS-6775) and its N-acetyl metabolite (EGIS-7649) from human plasma. The separation of the investigated compounds and internal standard was achieved on a Nucleosil 7 C(18) column with 2 mM heptanesulphonic acid containing 0.04 M phosphoric acid-acetonitrile-methanol (70:25:5, v/v), pH 2.

The effect of combined pre-treatment on the metabolism of antipyrine in the rat.

Determination of the effect of the known enzyme-inducers phenobarbital-Na and spironolactone on the activity of the MFO was carried out. Male Wistar rats were treated either with 40 mg/kg phenobarbital-Na or 40 mg/kg spironolactone, and also in combination with 100 mg/kg of the MFO was inhibitor alpha-methyldopa. The activity of the MFO was assessed by changes in antipyrine half-life.

Polymorphic paracetamol conjugation: phenotyping in a Hungarian population.

The authors studied the distribution of the paracetamol conjugation in a Hungarian population (53 adult Caucasian persons). The data indicated that the excretion of paracetamol glucuronide and sulphate were not normally distributed. Bimodality were apparent in both conjugation pathways: 15.

TxA2-PGI2-PGF2 alfa responses in the kidney to blood pressure reduction induced by vasodilator/vasorelaxing agents with different action in patients with essential hypertension.

In blood pressure (BP) reduction induced by gallopamil, hydralazine and prazosin in patients with essential hypertension a common trend was found in renal prostanoid production which included increased TxB2 excretion and/or augmented TxB2/6-keto-PGF1alfa ratio and, with the exception of response to prazosin, enhanced PGF2alfa excretion. Role of direct biochemical actions by the drugs in these responses was excluded by in vitro experiments with kidney slices from rats. The clinical and in vitro experimental findings suggested a mediator role of sympathetic activation but not that of the increased renin release in the urinary eicosanoid responses.

Human paraoxonase polymorphism: Hungarian population studies in children and adults.

The paraoxonase phenotype distribution pattern was studied in a Hungarian population of 102 children and 100 adults. All the subjects were of Caucasian origin and are not related. The adult population showed the trimodality in phenotype distribution similar to other European population data.

[Determination of paracetamol in urine by liquid chromatography].

Since the biotransformation of paracetamol (Acetaminophen) is practically confined to conjugation, the quantitative determination of paracetamol excretion may provide important information on phase II of the drug metabolism. We elaborated a simple and rapid liquid chromatographic method for the assessment of paracetamol and its conjugated metabolites in the urine to be available for routine use in the clinicopharmacological laboratory. The persons involved in the trial were administrated 500 mg of paracetamol to be taken on an empty stomach in the morning.

Clinical pharmacology in Hungary: past, present and future.

The authors outline the development of the clinical pharmacological network in Hungary. They describe some problems encountered during the development and discuss future plans.

Pantothenic acid, acute ethanol consumption and sulphadimidine acetylation.

The effect of pantothenic acid and acute ethanol loading on the genetically determined N-acetyltransferase activity has been studied using sulphadimidine as a test substance. The administration of 1100 mg pantothenic acid daily (600 mg orally, 500 mg iv) for seven days did not significantly alter sulphadimidine kinetics in the primarily elderly 21 subjects we investigated. Acute ethanol loading (0.

Simple high-performance liquid chromatographic method for the determination of tolbutamide and its metabolites in human plasma and urine using photodiode-array detection.

A high-performance liquid chromatographic method has been developed for the determination of tolbutamide and its metabolites in human plasma and urine. The compounds examined were extracted with diethyl ether from the acidified biological fluid. Chlorpropamide was used as internal standard, and 235 nm was chosen as the wavelength for diode-array detection.

Relation of renal thromboxane A2 production to urine flow, electrolyte excretion and plasma renin activity in control state and drug induced hypotension.

The functional importance of renal TxB2 generation in the maintenance of elevated arterial blood pressure in essential hypertension was followed in 22 patients, using the method of sustained blood pressure decrease by i.v. sodium nitroprusside infusion.