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Biomedical subjects

M Alvinerie

Publications and source records attributed to M Alvinerie.

At least 19 recordsLinked to original sources
PubMed1992

Ontogenic development of liver progesterone metabolism in female sheep. Contribution of cytochrome P4502B and P4503A subfamilies.

Age-related changes in progesterone hepatic metabolism were measured in Lacaune ewes in the foetal, neonatal (1 and 4 weeks), growing (7 months), pregnant (11 months) and adult (6 years) stages. 6 beta-Hydroxylation and 20 alpha-reduction were found to be the most efficient metabolic process in ovine microsomes. These activities were detected in 3-month-old foetuses and they increased rapidly during the first month of life, in a similar manner to the developmental expression of the cytochrome P4503A subfamily. 16 alpha- and 21-hydroxylation of progesterone were characterized by low, constant turn over in sheep liver microsomes during development. The hepatic ovine P4502B isozyme was purified to electrophoretic homogeneity by means of successive DEAE cellulose, hydroxylapatite and CM cellulose chromatographic separations. This hemoprotein had an apparent molecular weight of 51 kDa and was characterized by spectral data, NH2-terminal amino-acid sequence, immunological and catalytic properties. The relative contribution of this form and of the previously purified ovine P4503A subfamily was investigated in liver progesterone metabolism by immunoinhibition studies using polyclonal antibodies raised in rabbits and from the existence of induction and of significant correlations between microsomal activity and specific P450 content. In sheep liver microsomes, it would appear that cytochrome P4502B is involved in progesterone 21-hydroxylation whereas P4503A participates in the 6 beta- and 16 alpha-hydroxylation and possibly in the reductive conversion of progesterone in its 20 alpha-hydroxy derivative.

Aging↗
PubMed1991

Inducing effect of oxfendazole on cytochrome P450IA2 in rabbit liver. Consequences on cytochrome P450 dependent monooxygenases.

Male New Zealand rabbits were dosed with either 0.9, 4.5 or 22.5 mg/kg/day of oxfendazole by gastric intubation for 10 days. Oxfendazole administered at the therapeutic dose (4.5 mg/kg) and at the highest dose (22.5 mg/kg) increased 1.54- and 2.36-fold the total liver microsomal cytochrome P450 and more particularly the isoenzyme P450IA2 (95 and 184% increases) as demonstrated by western blotting. Increases in ethoxyresorufin O-deethylation and hydroxylations of benzopyrene and acetanilide occurred in livers of the same animals without any change in N-demethylation of aminopyrine, benzphetamine or erythromycin. Because of the unchanged level of mRNA specific to cytochrome P450IA2, as shown by northern blot analysis of poly mRNA, an enzyme stabilization rather than a transcriptional activation of IA2 genes should be involved in the P450IA2 regulation mechanisms. Oxfendazole bound strongly to cytochrome P450, giving rise to a type II spectrum, and inhibited noncompetitively the ethoxyresorufin O-deethylase and acetanilide hydroxylase activities, this confirmed that oxfendazole interacts only with the P450IA2 family. On the basis of a comparison of the enzymatic activities induced by various imidazole drugs, it was concluded that oxfendazole, like omeprazole and albendazole, behaved as a 3-methylcholanthrene-type inducer. These three benzimidazoles did not all belong to the same category of cytochrome P450 inducers as the antifungal drugs miconazole, clotrimazole and ketoconazole.

Animals↗
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

Pharmacokinetics of ampicillin and pentobarbital in the course of subclinical fascioliasis in sheep.

Pharmacokinetics of two common veterinary drugs, ampicillin and pentobarbital, were determined in sheep before and four, eight, 12, 17 and 21 weeks after infestation of animals by an oral administration of 150 metacercariae of Fasciola hepatica. The parasite infestation was ascertained by clinical observation of the animals. The pharmacokinetics of ampicillin were not significantly affected by the liver parasitism but the disposition of pentobarbital changed. A significant increase in elimination half-life (around 180 per cent), volume of distribution (130 per cent) and mean residence time (154 to 170 per cent) was observed in sheep infected by the parasite for four to 12 weeks. In these animals, duration of narcosis caused by pentobarbital was prolonged 1.8-fold. The results suggested that both reduced elimination of pentobarbital and impaired distribution of the drug would be responsible for the prolonged duration of narcosis in infected animals.

Ampicillin↗
PubMed1991

Plasma protein binding of nitroxynil in several species.

The binding of nitroxynil to total plasma proteins of cows, sheep and rabbits was characterized using equilibrium dialysis. The data indicate clearly that nitroxynil was highly (97-98%) bound to plasma protein of each animal. This linear binding would be due to the particular power exerted by serum albumin. The results are in good agreement with known pharmacokinetic properties of nitroxynil in domestic species.

Animals↗
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↗
PubMed1991

[Comparative pharmacokinetics of triclabendazole in camels and sheep].

The authors describe the compared pharmacokinetics of triclabendazole in three camels and four sheep which were given orally a single dose of 10 mg/kg liveweight. Plasma concentrations of triclabendazole and its main metabolites were determined by high performance liquid chromatography. No parental drug was detected in the blood plasma due to a hepatic first passage effect. It appeared that there was a major difference between the two species, triclabendazole sulfoxide concentrations being two times lower in camels than in sheep.

Animals↗
PubMed1990

Pharmacokinetics of prednisolone in children with the nephrotic syndrome.

The aim of this study was to establish whether the criteria for the clinical effectiveness of steroids are correlated with the pharmacokinetics of prednisolone in children treated with prednisone during an attack of idiopathic nephrotic syndrome (INS). Thirteen patients with nephrosis were included. Prednisolone, prednisone and cortisol levels were measured using a specific high-performance liquid chromatography assay after an oral dose of 1 mg/kg body weight of prednisone taken at the onset of the disease. All the pharmacokinetic parameters, including the conversion of prednisone to prednisolone were similar to the data already published in children with INS. No correlation was found between the values of pharmacokinetic parameters and criteria of clinical effectiveness. Hypo-albuminaemia was significantly correlated with the area under the plasma-concentration curve but not with the elimination half-life of prednisolone. Moreover, the prednisolone elimination half-life correlated with the urinary excretion of 17-hydroxycorticosteroids achieved in the first 6 h. The present study suggests that routine measurements of prednisolone kinetics do not help when assessing the treatment of children with INS.

17-Hydroxycorticosteroids↗
PubMed1990

Simultaneous measurement of prednisone, prednisolone and hydrocortisone in plasma by high performance liquid chromatography.

The authors describe a normal phase liquid chromatographic assay suitable for therapeutic monitoring of prednisone, prednisolone, hydrocortisone in human and animal plasma. The compounds were extracted into dichloromethane using flumethasone as internal standard. The separation was obtained by using a silica normal phase (5 mu) and a mobile phase of dichloromethane, methanol, acetic acid (95.6; 4; 0.4 v/v/v). The absorbance of the compounds was monitored at 254 nm with a sensitivity limit of 2 ng/ml for all the products. This method was applied to pharmacokinetic studies in animal and therapeutic monitoring in man.

Chromatography, High Pressure Liquid↗
PubMed1989

Stimulation of kappa opiate receptors in intestinal wall affects stress-induced increase of plasma cortisol in dogs.

In dogs, an acoustic stress (A.S.) produced by hearing of intense music (less than or equal to 90 dB) through earpieces for 1 h induced a 520% maximal rise in plasma cortisol 15-30 min after the beginning of stress. Oral administration of the specific kappa agonists, U-50488 (0.1 mg/kg) and PD 117302 (0.05 mg/kg), 30 min before the A.S. session reduced significantly (P less than 0.01) by 71.2% and 80.9% the maximal increase of plasma cortisol but did not affect the increase observed after intracerebroventricular administration of ovineCRF (100 ng/kg). These effects which are not reproduced by intravenous administration of the drugs at similar doses, were blocked by previous treatment with MR 2266 (0.1 mg/kg) or local anesthesia and vagotomy, suggesting that kappa opioid agonists inhibit the stress-induced activation of the hypothalamo-pituitary-adrenocortical (HPA) system by acting selectively on specific receptors located in the wall of the proximal gut.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Comparative incidence of experimental fascioliasis on corticosteroid pharmacokinetics in sheep.

1. The kinetics of intravenously administered prednisone (0.5 mg/kg) and methylprednisolone hemisuccinate (4 mg/kg) were compared in two groups of four young male sheep before and regularly after experimental infestation with 150 metacercariae of Fasciola hepatica and 5 or 7 weeks following a flukicidal treatment administered post-infection at week 25. 2. Parasitic pathology was ascertained by clinical observation and by the increase in plasma antibodies directed against liver flukes. 3. The disposition of prednisone was altered with a significant decrease of plasma clearance occurring from eleven weeks after infection onwards. This change was parallel to an increase in the mean residence time of prednisone and of its major metabolite (prednisolone). 4. The same parasitic burden provoked only a slight decrease in the elimination half-life of methylprednisolone alcohol when its hemisuccinate ester was administered.

Animals↗
PubMed1989

Vagally mediated inhibition of acoustic stress-induced cortisol release by orally administered kappa-opioid substances in dogs.

The effects of oral vs. iv administration of kappa- and mu-opioid agonists on plasma cortisol release induced by acoustic stress (AS) were evaluated in fasted dogs with an implanted jugular catheter. AS was induced by 1 h of music (less than or equal to 86 decibels) played through earphones and was accompanied by a 382% maximal rise in plasma cortisol after 15-30 min. Administered orally 30 min before the AS session, both U-50488 (0.1 mg/kg) and PD 117-302 (0.05 mg/kg) significantly (P less than or equal to 0.01) decreased (by 71.2% and 80.9%, respectively) the maximal increase in plasma cortisol induced by AS, while bremazocine, morphine, as well as iv administration of U-50488 at similar doses were ineffective. The effects of U-50488 and PD 117-302 orally administered (0.1 mg/kg) on the hypercortisolemia induced by AS were abolished by pretreatment with iv naloxone (0.1 mg/kg) or MR 2266 (0.1 mg/kg). Naloxone given alone significantly (P less than 0.01) increased basal plasma cortisol, without affecting cortisol increase induced by AS. Vagotomy abolished the effects of orally administered U-50488 on the AS-induced increase in plasma cortisol. Neither U-50488 nor PD 117302 (0.1 mg/kg, orally) reduced the increase in plasma cortisol induced by intracerebroventricular administration of ovine CRF (100 ng/kg). It is concluded that kappa- but not mu-opioid agonists are able to inhibit the stimulation of the hypothalamo-pituitary-adrenocortical axis induced by AS by acting selectively on peripheral kappa-receptors located in the wall of the proximal gut. This action is neurally mediated through afferent vagal fibers affecting central nervous system release of CRF induced by a centrally acting stressor.

Administration, Oral↗
PubMed1988

Prednisolone binding to plasma proteins in domestic species.

The binding of prednisolone to total plasma proteins of dogs, horses, cows, and sheep was characterized using equilibrium dialysis. Prednisolone was bound to a first protein with high affinity but low capacity (transcortin) and to a second protein according to a nonsaturable mechanism (albumin). Interspecies differences were observed, with cows and dogs exhibiting the lowest, and sheep and horses the highest specific binding capacities. The results are in good agreement with known pharmacokinetic properties of prednisolone in domestic species.

Animals↗
PubMed1988

Diurnal and episodic variations of plasma hydrocortisone concentrations in horses.

Using a specific high-performance liquid chromatographic technique, plasma hydrocortisone values were measured hourly in 6 horses and every 10 minutes in 4 horses over 24 hours. Both circadian and episodic variation was observed. The mean plasma hydrocortisone concentration was a maximum of 58.8 +/- 9.54 ng/ml at 9.19 +/- 0.59 hr and a minimum of 27.85 +/- 6.85 g/ml at 21.19 +/- 0.59 hr. The number of episodes of secretion was 10.0 +/- 1.41; the mean amplitude and duration of peak were 26.21 +/- 3.71 ng/ml and 105.25 +/- 21.24 min respectively.

Animals↗
PubMed1988

Hydrocortisone secretion: production rate and pulse characterization by numerical deconvolution.

Based on serial blood sampling over 24 h, hydrocortisone was shown to be secreted episodically in the horse. The purpose of the present experiment was to characterize peaks and troughs by analyzing the instantaneous secretion rate profile obtained by a deconvolution technique rather than from the plasma concentration time profile. Kinetic parameters of hydrocortisone were determined following intravenous bolus and intravenous perfusion of hydrocortisone. Stationary and nonlinearity of hydrocortisone disposition were demonstrated. With the use of clearance values calculated from constant perfusion administration, the 24-h hydrocortisone production rate was estimated at 0.46 +/- 0.08 mg.kg-1.24 h-1. The instantaneous secretory profile was reconstituted by deconvoluting the plasma concentration profile using structural parameters determined from the bolus hydrocortisone administration. When this secretory profile was subjected to a pulse analysis program, the number of detected peaks was found to be 17.25 +/- 1.26 and the mean peak duration 34.01 +/- 5.52 min. The total duration of secretory activity was estimated at 582.5 +/- 63.97 min. By comparison, when the plasma concentration profile was analyzed directly, the number of peaks was only 10.0 +/- 1.41 but their mean duration was much longer, i.e., 105.25 +/- 21.24 min. The origin of these differences and the advantages and limits of deconvolution analysis are discussed.

Animals↗
PubMed1988

CNS blockade of acoustic stress-induced gastric motor inhibition by kappa-opiate agonists in dogs.

The influence of the kappa-opioid substances dynorphin-(1-13), ethylketocyclazocine (EKC), and U 50488 and mu-opioid substance [D-Ala2-N-Me, p-nitro-Phe4-Gly5-ol]enkephalin (DAGO) on gastric motor inhibition induced by acoustic stress (AS) was investigated in fasted dogs with strain-gauge transducers chronically implanted on the antrum and proximal jejunum. AS induced by 1 h of music (80-90 dB) was delivered through earphones. Starting 40-50 min after the last migrating motor complex (MMC), AS delayed by 114% the occurrence of the next gastric MMC, whereas intestinal motility was unaffected. During AS plasma cortisol increased (P less than 0.05) by 215%, 15 min after the beginning of noise and reached a peak at 30 min. When administered intracerebroventricularly at doses higher than 20 ng/kg, dynorphin abolished the AS-induced lengthening of the gastric MMC cycle. Similar blockade was observed for EKC and U 50488 at doses of 10 and/or 20 ng/kg, but DAGO was unable to affect the AS-induced gastric inhibition at any dosage tested (20-200 ng/kg icv). At doses effective against AS-induced hypomotility, both dynorphin-(1-13) and EKC reduced significantly (P less than or equal to 0.05) the associated maximal increase in plasma cortisol level. Plasma cortisol was unmodified by intracerebroventricular administration of DAGO. None of the agonists affected basal plasma cortisol levels or the increase (0-90 min) in response to intravenous adrenocorticotropic hormone (ACTH, 5 IU). Both EKC (50 ng/kg) and U 50488 (20 ng/kg) were unable to antagonize the inhibitory effect of ovine corticotropin-releasing factor (CRF, 100 ng/kg icv).(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗