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Y Plusquellec

Publications and source records attributed to Y Plusquellec.

17 recordsLinked to original sources
PubMed1992

Application of a pharmacokinetic model with multiple enterohepatic cycles to a new inotropic drug after infusion and oral administration.

A pharmacokinetic model with multiple, unequal, enterohepatic recirculations was developed to fit the experimental data of a new inotropic drug after intravenous infusion and oral administration. Optimized model parameters were used to derive theoretical values of the area under the curves of concentration versus time that were in good agreement with the experimental values.

Administration, Oral↗
PubMed1992

Drug recirculation model with multiple cycles occurring at unequal time intervals.

A pharmacokinetic model for enterohepatic recycling has been developed to take into account multiple recirculations likely to occur at various times after intravenous or subcutaneous injection, after infusion, or after a single oral administration of a drug. The times when the gall bladder empties, the duration of infusion and the number of recirculations may be arbitrarily chosen (for simulations) or computed (for optimization) to express the concentration in the central compartment at any time. Without a new theoretical calculation, the area under the concentration curve may be obtained as a function of the model parameters. As an example, the model is applied to an experimental case of four recirculations after oral administration and to a new drug data fitting.

Administration, Oral↗
PubMed1991

Simultaneous pharmacokinetic modeling of a drug and two metabolites: application to albendazole in sheep.

Albendazole pharmacokinetic parameters were determined in lambs after iv, oral, and intraruminal single administrations. The parent drug and two metabolites, albendazole sulfoxide and albendazole sulfone, were simultaneously determined in whole blood, plasma, and urine using an HPLC method. The parent drug was only recovered in plasma when injected intravenously. For other routes, only the two metabolites were detectable; they were present in red blood cells and plasma at equal concentrations. The pharmacokinetic parameters were determined by using compartmental models which simultaneously described the two oxidative steps and the urinary excretion of the sulfoxide derivative. Dose-dependent pharmacokinetics was studied in the dose range 0.95-3.8 mg/kg. The results showed that clearance remained constant within the tested dose range since the area under the curve normalized to the dose was similar in the cases of sulfoxide and sulfone metabolites, whatever the route of administration. The drug appeared to be extensively metabolized in the body regardless of the route of administration. Sulfoxidation probably took place in liver, but other tissues seemed to be responsible for the formation of the sulfoxide which has been described as the major anthelmintic derivative of albendazole.

Administration, Oral↗
PubMed1991

Pharmacokinetic modeling of plasma and cerebrospinal fluid methotrexate after high-dose intravenous infusion in children.

A pharmacokinetic study was performed in plasma and cerebrospinal fluid (CSF) of patients suffering from brain tumors to describe the disposition of methotrexate. An open three-compartment model was developed to fit together the data obtained in plasma and CSF. The pharmacokinetic parameters obtained by the model agreed with those obtained with classical analysis and the fitting correctly depicted the plasma and CSF concentration decays. According to the results, such a model could be applied to other anticancer drugs.

Adolescent↗
PubMed1991

Relationship between loading dose and infusion rate to achieve any fraction of the steady-state level in any compartment model.

When a drug is infused at a constant rate K0, the time necessary for the concentration to reach a satisfying threshold of effectiveness may be too long. To achieve this level faster, it is useful to give simultaneously a dose D, of the same drug by intravenous injection. This paper proposes the calculation, as a function of K0 and model parameters, of the loading dose D necessary to reach, in a time T, any fraction of the asymptotic value of the amount of drug in a compartment receiving a constant rate infusion, for any n-compartment model. As an example, the expression of D for mammillary and catenary pharmacokinetic models is derived.

Body Fluid Compartments↗
PubMed1991

Teniposide and cisplatin given by intraperitoneal administration: preclinical and phase I/pharmacokinetic studies.

Cisplatin and teniposide given by intraperitoneal (IP) route exert a synergistic therapeutic effect against ascitic P388 leukemia in mice. As single agents, they display different dose-limiting toxicities and favourable pharmacokinetic characteristics in IP phase I trials. We administered cisplatin (fixed dose: 200 mg/m2) and teniposide (escalating doses) by IP route without dwell-time to investigate the toxicity, pharmacokinetics and clinical activity of this 2-drug combination. Nine patients received a total of 14 courses. Myelosuppression, nausea and vomiting were the most frequent toxicities. Leukopenia was the dose-limiting toxicity. The maximum tolerated dose of teniposide was 100 mg/m2 when administered with a fixed dose of 200 mg/m2 cisplatin. Pharmacokinetic analysis showed that the main parameters of both cisplatin and teniposide in the peritoneum and in the plasma were not modified when the drugs were combined. It appears that a pharmacodynamic interaction exists between cisplatin and teniposide which results in increased hematologic toxicity. Although an objective response has been observed in one patient with refractory ovarian cancer, such association should not be applicable for further clinical development due to marked toxicity and the low dose of teniposide recommended.

Adult↗
PubMed1991

Decrease in albendazole sulphonation during experimental fascioliasis in sheep.

1. The in vivo S-oxidation of albendazole was measured from the pharmacokinetic profile of albendazole sulphoxide and sulphone determined in young male sheep receiving oral albendazole (1.9 mg/kg). Studies were carried out before, and each month after, oral infestation by 150 metacercariae of Fasciola hepatica. 2. Parasitic pathology was ascertained by clinical observation of animals, and the increase in plasma antibodies directed against liver flukes. 3. Rate of conversion of sulphoxide to sulphone and rate of sulphone elimination, were respectively decreased by 47% and 87% at week 8 post-infection, whereas significant increases in the area under plasma sulphone concentrations versus time curve and mean residence time, occurred 4-12 weeks following the infestation. 4. A 58% decrease in albendazole sulphonation was demonstrated in liver microsomal preparations obtained from 8-week-infected sheep, while there was no change in the FAD-directed sulphoxidation of albendazole. 5. The transient impairment of albendazole sulphonation could be related to the decrease in liver microsomal cytochrome P450-dependent monooxygenases observed in sheep with a similar parasitic pathology.

Administration, Oral↗
PubMed1990

Analytical study of open four compartment pharmacokinetic models: concentrations, area under curves, mean residence times.

The analytical expressions for drug concentrations in each of the four compartments of different pharmacokinetic models, following any type of drug administration, are obtained from the transfer and elimination coefficients. In addition, areas under concentration curves and mean residence time of the drug, in a given compartment or in the whole system, are derived.

Administration, Oral↗
PubMed1990

Compartmental mean residence time in a mammillary model with an effect compartment after intravenous or oral administration.

A general estimation of mean residence time (MRT) in an effect compartment E, associated with a linear mammillary n-compartment model is presented: elimination takes place from the central and the effect compartments. Even though no sample is available from E, the MRT of the drug in this compartment can be estimated after intravenous or oral administration. Furthermore, the effect of MRT is independent of the route of administration. Also, with no new calculation, the method provides the area under the amount-time curve in compartment E.

Absorption↗
PubMed1989

A pharmacokinetic model for intraperitoneal administration of drugs: application to teniposide in humans.

A pharmacokinetic study of teniposide after ip administration with a 4-h dwell time was performed in patients suffering from abdominal malignant ascites. A three-compartment open model was developed to fit together the data obtained in plasma and peritoneum. The pharmacokinetic parameters obtained by the model agreed with those obtained by model-independent analysis, and the fitting correctly depicted the plasma and peritoneal concentration decays. According to the results, such a model could be applied to ip administration of anticancerous drugs.

Adolescent↗
PubMed1989

Analytical study of three-compartment pharmacokinetic models: concentration, area under curves, mean residence time.

The analytical expression for the drug concentration in each of the three compartments of a pharmacokinetic model, following any type of administration, is obtained from the transfer or elimination coefficients alone, without numerical approximation. Important applications of this result are the fitting of experimental data and the calculation of the areas under concentration curves or of the mean residence time of the drug in a given compartment or in the system as a whole.

Humans↗
PubMed1989

Phase I/pharmacokinetic study of intraperitoneal teniposide (VM 26).

A phase I/pharmacokinetic study of the i.p. administration of teniposide (VM 26) was undertaken. Eighteen patients with various malignancies and refractory malignant ascites consented to enter this trial. The dose escalation was made according to the modified Fibonacci scheme. Twenty-four courses were evaluable for toxicity, response and pharmacokinetics. The maximum tolerated dose was reached at 450 mg/m2 and the limiting toxicity was myelosuppression, principally leukopenia. Abdominal pain occurred in one half of the courses but was not limiting. No partial remission, but two 'no change' were achieved for more than 2 months. A reduction or disappearance of ascites was seen in two patients. Pharmacokinetic studies, carried out in all courses, showed that the total exposure for peritoneal cavity averaged 10-fold greater than that of plasma. Based on the outcome of this phase I study, we could recommend phase II studies at a dose of 390 mg/m2 i.p. repeated every 4 weeks with a 4 h dwell-time.

Abdominal Neoplasms↗
PubMed1988

Pharmacokinetics of veralipride after chronic administration in humans.

A pharmacokinetic study of veralipride (N-[(1-allyl-2-pyrroli dinyl)methyl]-5-sulfamoyl-o-veratramide) was performed in healthy volunteers during a chronic administration. The pharmacokinetic model based on the hypothesis of a double site for drug absorption, previously used after a single-dose oral administration, was developed to fit the data obtained after chronic administration. The empirical model used allows correct depiction of the behavior of the drug in the body, especially secondary peaks. According to the results, veralipride pharmacokinetics did not show any change upon chronic administration.

Adult↗
PubMed1987

A double-peak phenomenon in the pharmacokinetics of veralipride after oral administration: a double-site model for drug absorption.

Equal doses of veralipride have been given to 12 healthy volunteers by three different administrations--intravenous infusion, oral solution, and oral capsules--in a randomized cross-over design. After the intake of the solution, but not after infusion or capsules, two maximum plasma concentrations have been observed and interpreted, according to a double-site model for drug absorption.

Administration, Oral↗