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Biomedical subjects

J Heykants

Publications and source records attributed to J Heykants.

At least 109 records · Page 6Linked to original sources
PubMed1980

Intramuscular haloperidol decanoate for neuroleptic maintenance therapy. Efficacy, dosage schedule and plasma levels. An open multicenter study.

Thirty-eight hospitalized chronic psychotic patients were injected (i.m.) every 4 weeks with haloperidol decanoate using different dosage schedules which were calculated from the previously prescribed daily oral dose of haloperidol multiplied by a factor of 30, 20 or 10. The 20-fold schedule appeared to be adequate in most of the patients. All patients were well stabilized on their optimal dose schedule and several symptoms improved even further during treatment. No increase of extrapyramidal or other side-effects was reported in any of the patients. Antiparkinson medication could be omitted in 37 patients without problems. There was neither pain nor irritation at the site of injection. Plasma levels of haloperidol reaching a steady state after the second injection of haloperidol decanoate were about two times higher than during the previous oral treatment with haloperidol. No accumulation was observed. Haloperidol decanoate injected every 4 weeks proved to be as safe and therapeutically reliable as orally administered haloperidol.

Adult↗
PubMed1979

Simultaneous gas chromatographic determination of lorcainide hydrochloride and three of its principal metabolites in biological samples.

A method is described for the determination of the antiarrhythmic drug lorcainide hydrochloride and its three main metabolites in plasma, urine, faeces and tissues from man and animals. The procedure involves the extract of the parent drug, its metabolites and the internal standard from the biological materials at different alkaline pH values, back-extraction into sulphuric acid and re-extraction into the organic phase (heptane--isoamyl alcohol). After silylation of the different phenolic and the N-dealkylated metabolites, analyses were carried out by automated gas--liquid chromatography with electron-capture detection. The method has a sensitivity limit of 5 ng for lorcainide, and 10--20 ng for the various metabolites, per millilitre of plasma. The method was applied to urine, faeces, plasma and tissue samples from man and animals. It was also suitable for automatic sample analysis.

Acetanilides↗
PubMed1979

Steady-state plasma levels of flunarizine in chronically treated patients.

Plasma levels were measured at different times during long-term flunarizine treatment (duration 1--45 months, median: 6 months) of 50 patients with intermittent claudication. The dose was gradually reduced, within one month, from an initial dose of 30 mg daily to a maintenance dose of 10 mg daily. Plasma levels, measured by HPLC-method, showed considerable individual differences, ranging between less than 0.02 microgram/ml and 0.25 microgram/ml. Levels between 0.05 and 0.1 microgram/ml were found in 46% of the patients. Individual measurements clearly showed dose-related plasma-levels. There were no signs of accumulation. Side-effects were related to the dose rather than to the levels. There was no correlation between clinical improvement and plasma levels. An extensive first-pass metabolism in the liver is suggested as a possible explanation for the varying inter-individual plasma levels.

Adult↗
PubMed1978

Domperidone, a novel and safe gastrokinetic anti-nauseant for the treatment of dyspepsia and vomiting.

The new potent anti-nauseant 5-chloro-1-(1p[3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-propyl]-4-piperidinyl)-1.3-dihydro-2H-benzimidazol-2-one (domperidone), which in contrast to available anti-emetics does not provoke extrapyramidal or adrenolytic adverse effects, also enhances gastric emptying motility. Controlled clinical trials have confirmed its prokinetic effects on the stomach and its lack of side-effects, even at high doses. This anti-nauseant appears to be a safe and effective treatment for patients, both adults and children, with dyspepsia or vomiting.

Animals↗
PubMed1977

A sensitive radioimmunoassay for fentanyl. Plasma level in dogs and man.

Antiserum to fentanyl was obtained in rabbits repeatedly injected with carboxyfentanyl conjugated to bovine serum albumin. Using the antiserum, a highly sensitive radioimmunoassay has been developed, based on the dextran-coated charcoal method. It proved possible to assay the drug directly in plasma, in amounts as small as 30 picogram in 0.5 ml. The antibody was highly specific for fentanyl and no cross-reaction was observed with its major metabolites. This sensitive and specific radioimmunoassay method was employed to determine fentanyl in plasma from six volunteers after an intravenous bolus of 0.2 mg, and in plasma from dogs treated both intravenously and subcutaneously with 0.02 mg/kg. The plasma level of fentanyl could be followed for up to 6 h after a therapeutic dose in dogs and man.

Adult↗
PubMed1977

In vitro metabolism of lidoflazine by rat and dog liver fractions.

Lidoflazine was metabolized very rapidly by 16000 g supernatant fractions of rat and dog liver. The rate and the extent of metabolism were considerably superior for rat liver. Lidoflazine metabolites were purified by extraction and thin-layer chromatography and identified by mass spectrometry. The main pathways of the in vitro metabolism by rat and dog liver fractions were the same. Oxidative N-dealkylation was the most important. An incubation of major metabolite 1-[4,4-bis(4-fluorophenyl)-butyl]piperazine, with rat liver fraction was performed. A hydroxylated metabolite and a ketopiperazine metabolite were detected only in the dog experiments.

Animals↗
PubMedDate not supplied

Excretion and metabolism of lorcainide in rats, dogs and man.

After p.o. or i.v. administration of 3H-lorcainide, excretion of the radioactivity was almost complete within four days. In rats and dogs, about 35% of the dose was excreted in the urine and about 60% in the faeces. However, in humans, 62% was excreted in the urine and 35% in the faeces. In rats, about 70% of the orally administered radioactivity was excreted in the bile within 24 hours. Enterohepatic circulation was proven by "donor-acceptor" coupling in rats. Lorcainide was extensively metabolized. Urinary and faecal metabolites were isolated by extraction and high pressure liquid chromatography (HPLC), and characterized by chromatographic comparison with reference compounds, by mass spectrometry, and NMR. The mass balance for unchanged lorcainide and its major metabolites (determined by radio-HPLC) was very similar in the urine and faeces. Only minor quantitative differences were observed between intravenously and orally dosed animals, and between male and female rats. Major biotransformation pathways in the three species were: hydroxylation, O-methylation and glucuronidation. 4-Hydroxy-3-methoxy-lorcainide was the main metabolite. alpha-Oxidation resulting in alpha, 4-dihydroxy-3-methoxy-lorcainide, was observed in dogs only. Minor pathways were: oxidative N-dealkylation and amide hydrolysis. A remarkable 5-hydroxy-3,4-dimethoxy-metabolite was identified unambiguously in the three species.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetic-pharmacodynamic relationships in phase I/phase II of drug development.

Early investigation of pharmacokinetic-pharmacodynamic relationships in Phase I/II may facilitate the further clinical development of a new drug. Although some pharmacology assessments in Phase I are often only surrogates for the therapeutic effect, PK-PD modelling of those effects provides in general crucial information on the drug's potency in vivo. A mathematical PK-PD expression allows explorative simulations on the rate of onset of drug action, on the intensity and duration of the effects for doses in future clinical trials, or in situations of altered drug kinetics. Furthermore, understanding of the PK-PD relationship early on in drug development may anticipate unnecessary exposure of human subjects to inappropriate drug doses or trials.

Animals↗
PubMedDate not supplied

Itraconazole: pharmacologic studies in animals and humans.

Several pharmacologic studies of itraconazole, an orally active antifungal triazole, were conducted in humans and animals. In dogs and rats, no significant toxic effects were seen at doses of up to 40 mg/kg. Endocrinologic studies demonstrated that itraconazole, unlike ketoconazole, does not significantly affect human testicular and adrenal steroidogenesis. Pharmacokinetic studies indicated that itraconazole has a high tissue affinity and a longer half-life than ketoconazole. These pharmacologic observations suggest that itraconazole has a broader spectrum of activity than ketoconazole and a lower potential for producing adverse effects.

Adrenal Glands↗
PubMedDate not supplied

Study of the placental transfer of cisapride in sheep. Plasma levels in the pregnant ewe, the fetus, and the lamb.

The placental transfer of cisapride, a new prokinetic agent, was studied in a sheep model. The pharmacokinetics of cisapride were studied in the lamb, the pregnant ewe, and the fetus by obtaining blood samples from chronically implanted arterial catheters. Comparable pharmacokinetic parameters were found in the lamb and the adult sheep: half-life, 1.39-1.83 hr; total plasma clearance, 1998-2160 ml/kg/hr; AUC, 92.6-100.1 ng.hr/ml. Cisapride plasma concentrations after continuous infusion were predicted correctly based on the parameters obtained after iv bolus. There was a materno-fetal transfer of cisapride following a single iv bolus administered to the mother. Cisapride crossed the placenta within 5 min and equilibrated with maternal plasma within 20 to 30 min after dosing. The average fetal-to-maternal plasma concentration ratio was 0.71. The amniotic fluid also contained measurable amounts of cisapride. The protein binding of cisapride in maternal and fetal plasma is 89.0% and 88.4%, respectively; the free fraction is 4 times larger than in humans. Cisapride crosses the ovine placental barrier. The sheep placenta is less permeable than the human placenta, but the higher free fraction of cisapride facilitates placental transfer.

Amniotic Fluid↗