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Biomedical subjects

R Hendriks

Publications and source records attributed to R Hendriks.

32 records · Page 2Linked to original sources
PubMed1987

Pharmacokinetics and tissue distribution of the new gastrokinetic agent cisapride in rat, rabbit and dog.

The plasma kinetics and tissue distribution of the gastrokinetic (+/-)-cis-4-amino-5-chloro-N-[1-(3-(4-fluorophenoxy)propyl]-3-methoxy-4- piperidinyl]-2-methoxybenzamide monohydrate (cisapride, R 51 619) have been studied in the rat, rabbit and dog. After intravenous administration to rats (5 mg/kg) and dogs (0.63 mg/kg) plasma level-time curves were adequately fitted to a two-compartmental model. The plasma clearance (ClT) and volume of distribution (Vdss) averaged 91 ml/min.kg and 4.7 l/kg in the rat and 4.2 ml/min.kg and 0.82 l/kg in the dog, respectively. Following oral administration, cisapride was rapidly and almost completely absorbed from the gastrointestinal tract in rats and rabbits. The absorption was somewhat slower in the dog. In male rats the plasma radioactivity was mainly due to metabolites, unaltered cisapride representing on average 10% of the total radioactivity. A markedly larger proportion of the parent drug was seen in female rats. Linear plasma kinetics were observed for cisapride in the dose range of 10 to 160 mg/kg. Similarly in the dog, linearity was observed after oral administration in the range of 0.31 to 10 mg/kg. The plasma kinetics remained unaltered on repeated oral doses of 10 mg/kg to rats and subchronic intravenous administration at 0.63 mg/kg to dogs. Compared with intravenous administration, the absolute bioavailability of oral cisapride was 23% in rats and 53% in the dog for the drug given in solution. The terminal plasma half-life of cisapride was about 1-2 h in the rat and about 4-10 h in the rabbit and dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Radioimmunoassay of the new opiate analgesics alfentanil and sufentanil. Preliminary pharmacokinetic profile in man.

The development of two analogous radioimmunoassay (RIA) procedures based on dextran-charcoal separation is described for the quantification of two fentanyl-like analgesics, alfentanil and sufentanil. Immunization of rabbits with conjugates of bovine serum albumin and carboxy-derivatives of the respective drugs resulted in the production of antisera capable of detecting less than 0.05 ng ml-1 of the parent analgesics with high specificity and almost no cross-reactivity with major metabolites. Excellent agreement was obtained between RIA--without prior extraction--and gas chromatography for alfentanil concentrations in human plasma. Because of sufentanil's low therapeutic plasma levels, no comparison could be made between its RIA and an alternative assay, however, there was strong evidence for the specificity of the assay when applied directly to plasma. With these RIA methods preliminary information was obtained on plasma concentrations and elimination of alfentanil or sufentanil in patients given an intravenous bolus injection of 50 micrograms kg-1 of alfentanil, or 5 micrograms kg-1 of sufentanil. For both analgesics, the pharmacokinetic profile in man could be described by a three-compartment model. The terminal elimination half-life was 88 min for alfentanil and 140 min for sufentanil. Six hours after a therapeutic dose, plasma levels were in the order of 3 and 0.3 ng ml-1 for alfentanil and sufentanil respectively.

Alfentanil↗
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 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. 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↗
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↗