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M Hanocq

Publications and source records attributed to M Hanocq.

At least 37 records · Page 2Linked to original sources
PubMed1988

Pharmacokinetics and metabolism of hexamethylmelamine in mice bearing renal cell tumors.

The pharmacokinetics of hexamethylmelamine (HMM) and its main metabolites hydroxymethylpentamethylmelamine (HMPMM), pentamethylmelamine (PMM), and 2,2,4,6, tetramethylmelamine (2,2,4,6 TetrMM) were studied in renal cell (RC) tumor tissues and plasma of CDF1 mice that had received IP bolus injections of the maximally tolerated dose (200 mg/kg) of HMM. HMM, PMM, and 2,2,4,6 TetrMM concentrations determined in RC tissues were much higher than the plasma values, as indicated by the pharmacokinetic parameters (Cmax and AUC). On the other hand, very low levels of HMPMM, generally considered to be a potentially active antitumor compound, were detected in the target tissues, whereas this hydroxylated metabolite was stable and easily determined in plasma. High HMM concentrations in RC tissues could correlate with the high sensitivity of the tumor to this drug. However, the behavior of HMPMM remains unclear; related hypotheses are presented in this paper.

Altretamine↗
PubMed1986

Pharmacokinetics and metabolism of hexamethylmelamine in mice after IP administration.

The pharmacokinetics of hexamethylmelamine (HMM) and its first metabolite (hydroxymethylpentamethylmelamine: HMPMM) following IP bolus dose of 200 mg/kg were studied in mice. The drug concentrations were determined by a sensitive reversed-phase HPLC assay. Thus, for the first time, HMM major hydroxylated and demethylated metabolite plasma levels canbedetermined at the same time. Pharmacokinetic data were analyzed by an original method using a nonlinear cost function minimized by a simplex algorithm. An important property of this computer program is that convergence is ensured in contrast to linear or nonlinear least-square regression analysis, which leads to lack of convergence or to false convergence. Both HMM and HMPMM data fit a one-compartment open model. The parameters obtained indicate that the parent drug would probably be rapidly and completely transformed by the human body into HMPMM.

Algorithms↗
PubMed1983

Degradation study of catecholamines, indole amines and some of their metabolites in different extraction media by chromatography and electrochemical detection.

Optimal conditions for the extraction from brain tissue and the simultaneous quantification of catechol and indole derivatives were determined after a systematic degradation study in water and perchloric acid. The roles of three parameters, namely temperature, presence of antioxidant agents, and time, were considered. Adrenaline, noradrenaline, dopamine, homovanillic acid, 5-hydroxytryptophan, 5-hydroxyindole acetic acid, serotonin, and epinephrine were separated by HPLC and detected electrochemically. The results indicated a great instability of the indole derivatives at an ambient temperature, in an acid medium, and in the absence of a protective agent. Therefore, when perchloric acid has to be used for deproteinization, the lowest concentration (0.1 M) is preferable. The samples have to be kept on ice, in darkness, and protected by ascorbic acid and sodium ethylenediamine tetracetate.

Ascorbic Acid↗
PubMed1983

Plasma and erythrocyte zinc, copper and selenium in cystic fibrosis.

Plasma and erythrocyte zinc, copper and selenium were measured in 20 cystic fibrosis children, aged 7 to 19 years. Mean plasma zinc and copper levels were not different from those in age-matched controls but very low zinc levels occurred sporadically. Plasma zinc concentrations were significantly lower in patients with moderate-to-severe growth retardation and with severe pulmonary disease as compared to patients without growth failure and with moderate pulmonary disease. Mean erythrocyte zinc (40.8 micrograms/g Hb +/- 9.2) and copper levels (3.56 micrograms/g Hb +/- 0.50) were very significantly increased (30.4 micrograms/g Hb +/- 5.2 and 2.73 micrograms/g Hb +/- 0.30 respectively, for age-matched controls). Mean plasma and erythrocyte selenium levels (63 ng/ml +/- 15 and 329 ng/g Hb +/- 86) were significantly lower than those in age-matched controls (82 ng/ml +/- 13 and 404 ng/g Hb +/- 116). The trace element concentrations in erythrocytes are discussed in relation to the activities of the copper- and zinc-containing enzyme superoxide dismutase and the seleno-enzyme glutathione peroxidase. We consider that more data on trace element metabolism in CF should be collected before specific supplementation is considered.

Adolescent↗
PubMed1981

Toxicological analysis of phenylethylamines by high performance reversed-phase ion-pair partition thin-layer and liquid chromatographies.

A rapid and specific method was developed to identify phenylethylamines in urine. After an organic extraction at appropriate pH, reverse phase ion-pair partition chromatographies were used: a high performance thin-layer test followed by high performance liquid chromatography. The use and benefits of the procedure are described in detail and compared with other methods. In a very short time (10 min) the presence of phenylethylamine is detected on a thin-layer plate. In the case of positive result the product is then specifically identified by high performance liquid chromatography by means of a complete UV spectrum traced directly on the eluated compound. The sensitivity of the method is highly increased because the detection is operated at 215 nm.

Chromatography, High Pressure Liquid↗
PubMed1979

[Microdetermination of fluoride in human bones (author's transl)].

A spectrophotometric method (cerium(III)-alizarin complexan-fluoride in presence of 25% dimethylsulfoxyde) is described for the determination of fluoride in human bones. The anion is determined after separation by microdiffusion as hydrofluoric acid using Petri boxes without any mineralization. This analytical method is selective, accurate and rapid.

Bone and Bones↗
PubMedDate not supplied

Absorption and metabolism of oral zinc gluconate in humans in fasting state, during, and after a meal.

The absorption and metabolism of zinc in a commercial form for oral use (Rubozinc, 15 mg zinc as gluconate) were investigated in 10 subjects by a kinetic study of the serum zinc profile after administration of 45 mg zinc under three conditions: after an overnight fast, during a standardized breakfast, and 2 h after this meal. The pharmacokinetic parameters were calculated by a method suitable to the characterization of rebound effects (recycling of the element in the gastrointestinal tract). In fasting state, the parameters were comparable to those previously collected in the same subjects with oral 45 mg zinc as sulfate, except with very significantly higher Cmax and area under curve (AUC), showing a better bioavailability for zinc in the commercial form. The light meal perturbed the absorption process as evidenced by the significant increases in the lag time (+180%), the tmax (+57%), and the lag times for the first two cycles during the meal. However, the parameters returned to normal values 2 h after the meal. The Cmax only moderately decreased during the meal (31%) as did the AUC (-28%). An important delay in the absorption of zinc in the commercial form when taken during a meal was therefore demonstrated, but the effect on zinc bioavailability was only moderate.

Administration, Oral↗
PubMedDate not supplied

A new method to estimate parameters of pharmacokinetics with enterohepatic circulation.

A new method of estimating pharmacokinetic parameters for enterohepatic recirculation models is presented. The algorithm, based on the simplex method, assures a convergence toward the minimum minimorum; provides reliable parameters, even in large numbers; and handles up to five cycle effects in five established models: IV, EV, mono-, bi- or tricompartmental. For each model, the reabsorption rate may be considered to be slow (characterised by a rate constant with a significant value) or instantaneous (an infinite rate constant). Two examples are given to illustrate the qualities of the software that incorporates this new algorithm. The first relates to the pharmacokinetics of zinc orally given to humans; the second treats the kinetics of alpha-methylDOPA given to dogs intra-arterially (note: values of plasma concentrations have been extracted from the literature).

Enterohepatic Circulation↗
PubMedDate not supplied

A new algorithm for computing the parameters of linear compartment models in pharmacokinetics.

A new algorithm (FADHA) for computing pharmacokinetic parameter estimates has been developed. This technique is based on the simplex method which is used to minimize a nonlinear cost function. An important property of this program is that the convergence is ensured contrary to the well-known linear or nonlinear least-squares regression analysis which lead to a lack of convergence or to a false one. Two investigations of the comparative performances of FADHA program and other algorithms were undertaken (hexamethylmelamine and Piracetam pharmacokinetics). Least square analysis of data yielded biased estimates whereas FADHA estimates were unbiased and more precise. This new technique, takes into account all the possible observation errors and uses the concept of a weighting function rather than weights as such.

Altretamine↗
PubMedDate not supplied

Pharmacokinetics of daunorubicin and daunorubicinol in plasma, P388 and B16 tumours. Comparison with in vitro cytotoxicity data.

The comparison of pharmacokinetics of DNR in mouse plasma, in the DNR naturally resistant B16 melanoma and in the DNR naturally sensitive P388 leukemia showed that there is no direct correlation between total concentrations of this drug in tumours and the sensitivity resistance of these tissues. A finding which demonstrates the inadequacy of distribution models to select new potential anticancer drugs. Cytotoxicity of DNR and its metabolites to B16 melanoma and P388 leukemia cell lines were determined in vitro. Calculated inhibitory concentrations 50 (IC50) were compared to maximal concentrations determined by pharmacokinetic studies. In all cases in vitro IC50 were lower than Cmax values. Moreover, resistant cells in vivo were found to be sensitive to DNR and metabolites when they are propagated in vitro. Tissue concentrations, as well as in vitro data, were fitted to appropriate models by an original program (FADHA) which uses the simplex method to minimize a non-linear cost function. Best fit models were chosen by statistical criteria.

Analysis of Variance↗
PubMedDate not supplied

Pharmacokinetic study of orally administered zinc in humans: evidence for an enteral recirculation.

Starting from the experimental design of the established 'Zinc Tolerance Tests', the absorption and distribution of the essential trace element zinc in humans was investigated in 10 subjects by performing a pharmacokinetic study of the serum zinc profile after oral administration of a pharmacological dose of the metal, i.e. 0.69 mmol (45 mg) zinc as ZnSO4.7 H2O. The adopted experimental conditions include frequent measurements of serum concentrations, a total investigation time of 8 h after ingestion, and a correction of basal zinc levels taking into account the circadian variation. Rebound effects were evidenced in the time versus concentration curves showing a regular recycling of the element in the digestive tract. Estimation of the parameters by an original method allowed us to calculate the characteristics of the cycles. The first one occurred after 1.4 h, before the time needed for appearance of the maximum concentration which was around 2.3 h, and exhibited mean reabsorption of 70% of administered dose. The subsequent ones, maximum 5 during the investigation period, appeared at regular intervals of approximately 1.2 h, with a decrease in the quantity reabsorbed. These observations are consistent with the previously reported endogenous secretion of zinc, a physiological mechanism contributing to zinc homeostasis.

Absorption↗