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Biomedical subjects

M Michiels

Publications and source records attributed to M Michiels.

33 records · Page 2Linked to original sources
PubMed1982

The pharmacokinetics of mebendazole and flubendazole in animals and man.

A sensitive and specific radioimmunoassay procedure was developed for mebendazole and flubendazole enabling a more thorough study of the systemic absorption and pharmacokinetic behaviour of the drugs. In rats, plasma levels of oral and subcutaneous mebendazole were about 10 times higher than those of flubendazole. The pro-drug R 34 803 showed levels of metabolically formed flubendazole similar to those found for mebendazole. Intramuscular flubendazole in dogs, injected for 5 consecutive days, produced sustained fairly high plasma levels for at least 6 weeks after the last dose. The absorption of oral flubendazole in man was markedly enhanced when the drug was taken together with a meal. A 20-times higher dose, however, produced only an increase by 1.4 of the plasma levels and AUC-values, indicating that the absorption of flubendazole is limited by the extremely poor solubility of the drug in the contents of the gastrointestinal tract.

Animals↗
PubMed1981

On the pharmacokinetics of domperidone in animals and man. I. Plasma levels of domperidone in rats and dogs. Age related absorption and passage through the blood brain barrier in rats.

Domperidone, a novel gastrokinetic and antinauseant lacking central side-effects, was administered intravenously to male Wistar rats and orally to fasted rats of either sex and to 1- and 6-day old neonates at doses of 2.5 mg 14C-labelled drug/kg. The biphasic absorption of domperidone in fasted rats was extremely rapid suggesting a partial absorption from the stomach. The metabolism of domperidone was sex- and age-related: it was slower in the female rat and in the neonates. The elimination system for the metabolites was still immature in the 1-day old pups. The distribution of domperidone (and related metabolites) to the rat brain was limited, brain concentrations being lower than corresponding plasma levels in all cases. In 1-day old neonates, the blood-brain barrier was less obstructive to the passage of domperidone than in older rats. In Beagle dogs, domperidone pharmacokinetics were described by a two-compartment model with half-lives of distribution and elimination of 6 minutes and 2.45 hours respectively. The time-courses of the drug plasma levels were similar for single and repeated (once daily for 11 months) doses of 2.5, 10 and 40 mg/kg, indicating that chronic administration of domperidone, even at high dose levels, did not alter its pharmacokinetics. AUC-values increased proportionally with the dose pointing to linear pharmacokinetics over a wide dose range.

Age Factors↗
PubMed1981

On the pharmacokinetics of domperidone in animals and man II. Tissue distribution, placental and milk transfer of domperidone in the Wistar rat.

Tissue distribution, placental transfer and transition into milk of the gastrokinetic drug domperidone were studied in the Wistar rat after i.v. or p.o. administration of the labelled compound at 2.5 mg/kg. Whole-body autoradiography and liquid scintillation counting were used to investigate the tissue localization of domperidone in pregnant and non-pregnant rats. In fasted rats, tissue levels were maximal within 15 minutes after either route. In non-fasted animals peak time occurred 30 minutes after oral treatment. Large amounts of radioactivity were present in the stomach, and in the bilious contents of the intestine. High activity was further detected in the liver, kidney, lung and some glandular tissues. After a rapid initial decrease radioactivity was eliminated with a half-life of 8-10 hours. Except for brain and testes, plasma levels were markedly lower than corresponding tissue levels. At 1 hour placental levels were 2-2.7 times higher and foetal concentrations 2.1-2.5 times lower than maternal plasma levels. The placentae and foetuses predominantly contained unchanged domperidone. At peak time only 0.2 (i.v.) and 0.08% (p.o.) of the dose crossed the placenta. Blood levels were always lower than milk concentrations. Preferentially metabolites were excreted with the milk. After a 20-hour suckling period of orally dosed dams, 0.2% of the dose was recovered in the combined tissues of 6 suckling pups.

Administration, Oral↗
PubMed1981

On the pharmacokinetics of domperidone in animals and man III. Comparative study on the excretion and metabolism of domperidone in rats, dogs and man.

The excretion and metabolism of the novel gastrokinetic and antinauseant drug domperidone were studied after oral administration of the 14C-labelled compound to rats, dogs and man, and after intravenous administration to rats and dogs. Excretion of the radioactivity was almost complete within four days. In the three species, the radioactivity was excreted for the greater part with the faeces. Biliary excretion of the radioactivity amounted to 65% of the dose 24 hours after intravenous administration in rats. Unchanged domperidone as determined by radioimmunoassay, accounted in urine for 0.3% in dogs, 0.4% in man, and in faeces for 9% in dogs and 7% in man. The main metabolic pathways of domperidone in the three species were the aromatic hydroxylation at the benzimidazolone moiety, resulting in hydroxy-domperidone -the main faecal metabolite-, and the oxidative N-dealkylation at the piperidine nitrogen, resulting in 2,3-dihydro-2-oxo-1H-benzamidazole-1-propanoic acid the major radioactive urinary metabolite- and 5-chloro-4-piperidinyl-1,3-dihydro-benzimidazol-2-one. In urine the two first metabolites were present partly as conjugates. A mass balance for the major metabolites in urine, faeces, bile and plasma samples was made up after radio-HPLC (reverse-phase HPLC with on-line radioactivity detection) of various extracts. Only minor species differences were detected.

Adult↗
PubMed1981

On the pharmacokinetics of domperidone in animals and man. IV. The pharmacokinetics of intravenous domperidone and its bioavailability in man following intramuscular, oral and rectal administration.

The pharmacokinetics and bioavailability of domperidone, a novel gastrokinetic, were studied in healthy male subjects by comparing plasma concentrations and urinary excretion following intravenous, intramuscular, oral and rectal administration. Two oral dosage forms were studied: 10-mg tablets and a 10-mg/ml oral solution. The influence of a meal on the oral bioavailability and the dose-proportionality were also investigated. Plasma levels of intravenous domperidone could be described by a three-compartment model with a rapid distribution of 40% of the dose to a "shallow" peripheral compartment. The final elimination half-life was 7.5 hours. Peak plasma levels were reached within 30 minutes following intramuscular and oral administration and at 1-4 hours following rectal administration. Since domperidone showed an extensive first-pass elimination, AUC-values -a measure for the bioavailability- were considerably lower after oral than after parenteral administration. Equal oral and rectal doses gave a similar bioavailability. AUC-values increased proportionally with the dose over a 10-60 mg range. Cumulative urinary excretion of unchanged domperidone was proportional to corresponding AUC-values. The bioavailability was discussed in the light of the therapeutic results.

Administration, Oral↗
PubMed1980

Serum haloperidol determinations in psychiatric patients. Comparison of methods and correlation with serum prolactin level.

Twenty-one serum samples from 11 schizophrenic patients receiving long-term haloperidol therapy were analyzed for haloperidol concentrations by two different radioimmunoassays (RIAs) and gas chromatography (GC). There was a good correspondence between the RIA and GC values over a wide range of drug concentrations. However, compared with the specific GC technique, both RIA methods overestimated haloperidol concentrations, reflecting differences in the specificities of the two RIA antibodies. One of the RIA methods had the requisite specificity for application to patients treated with long-term haloperidol therapy, although further methodological refinement will be required for its general clinical application. Haloperidol values determined by GC and RIA analyses correlated highly with prolactin concentrations in the same samples, suggesting that the usefulness of prolactin measurement as an "in vivo bioassay" for circulating levels of haloperidol should be further explored.

Chromatography, Gas↗
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↗
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↗
PubMedDate not supplied

Tissue distribution and excretion of radioactively labelled compounds in the Wistar rat after administration of [N-methyl-14C]-erythromycin A.

Tissue distribution and excretion of radioactively labelled compounds was studied in the Wistar rat after i.v. administration of [N-methyl-14C]-erythromycin A. Whole-body autoradiography and liquid scintillation counting was used to investigate the tissue localization of radioactivity in pregnant and non-pregnant rats. Tissue levels were maximal within 20 min, except for lachrymal glands, thymus and brain. Large amounts of radioactively labelled compounds, partly originating from active secretion, were present in the small intestine and caecum. Marked concentration of radioactively labelled compounds was also observed in the liver, spleen, lachrymal and salivary glands, lymph nodes, mammary glands, skin, bone marrow, and, to a lesser extent, in the lung, kidney and skeletal muscle. During six hours of experimental follow-up, plasma levels remained lower than corresponding tissue levels. At 1 h the radioactivity in fetuses was about three times lower than that in maternal blood. Within 48 h, more than 90% of the administered radioactivity was excreted. The amounts of radioactivity recovered in urine, faeces and expired air were about 19%, 48% and 24% respectively. After 48 h, 8% of the administered radioactivity was found in the carcass.

Animals↗
PubMedDate not supplied

[Contribution of neo-electroencephalography in adult functional and psychiatric disorders].

Two comparative studies of the basic activity at rest, with closed eyes taken in conventional EEG and analysed in Neo-EEG are carried out in adults showing functional or psychiatric disorders. The first open study involves 18 subjects suffering from a affection called "neurodystony" and 24 depressed subjects. The second study made in double-blind compares the results of the conventional EEG with the Neo-EEG in 19 depressed patients, 28 alcoholic patients and 26 psychotic patients. The Neo-EEG discloses abnormalities in about 60% of the cases when the conventional EEG is normal. The conventional EEG as well as the Neo-EEG diagnose a greater number of low voltage in alcoholic subjects and clear abnormalities in psychotic subjects. Low voltage is never detected in psychotic patients. In depressives, the Neo-EEG shows about 65% of abnormalities of which an asymmetry of the basic frequency in the center of the two hemispheres when they are analysed separately. That asymmetry develops in parallel with the clinical state. The asymmetry is also found in psychotic patients. In nervous or neurodystonic subjects, the Neo-EEG only discloses 25% of abnormalities. The Neo-EEG appears as an easy method, able to detect dysfunctions which cannot be disclosed with the conventional EEG and useful to follow their developments. Moreover, the result of this technique brings to the fore abnormalities not detected with the conventional EEG: this eventually leads to prescribe other therapies than those initially considered.

Adolescent↗
PubMedDate not supplied

[MALT conjunctival lymphoma: how to treat?].

A case of conjunctival lymphoma belonging to the MALT tissue is reported hereby. It is very uncommon in the literature, but special tools are needed to recognize this conjunctival involvement: Frozen sections of tissue to perform immunocytochemical studies. Investigations of the other lymphoid tissue, to assess the localized feature of the conjunctival disease.

Conjunctival Neoplasms↗