Biomedical subjects
Publications and source records attributed to J Oustrin.
Oral administration of cadmium to female rats for 6 weeks does not reduce the microsomal cytochrome P450 levels in the liver and kidneys, nor the cytochrome P450 content in the renal mitochondria.
Calcium influx into rat intestine was investigated, in vitro, after cadmium chronic oral exposure. In active calcium transport, pretreatment by 1.25 dihydroxyvitamin D3 prevents the effect of cadmium on the maximal influx value Jm and leads to an increase of the half-saturation constant Kt.
In cadmium exposed Rats correlation analysis of calcium deep bone assessed by compartimental analysis and results of bone calcium determination by neutron activation shows a significative relationship between both values.
The radioisotopic study of calcium metabolism in the rat after chronic oral administration of cadmium (8 mg/kg) has shown two different effects: a) in the intestine cadmium inhibits the absorption of calcium by active transport; b) in the deep bone compartment, the decrease of the bone calcium used for the crystallization goes together with a reduction of the exchange rates between this compartment and the central compartment (serum extracellular and soft tissues calcium). The simultaneous oral administration of 1.25 dihydroxyvitamin D3 (80 ng/kg) even though it increases significantly the calcium intestinal absorption factor does not allow the various parameters of bone calcium metabolism to stay within normal values. In spite of the arrest of osteolysis and of an strong increase of osteogenesis (superficial bone balances and alkaline phosphatases) the loss of calcium caused by cadmium in the deep bone is not compensated.
The fate in the organism of Adenosine Monophosphate after a single oral administration of 10 mg/kg, was studied in the Rat, using 14C-labelled AMP. This paper deals more specially with the study of the plasmatic kinetics of AMP, since we proved at first that the AMP molecule goes intact through the intestinal barrier into the blood. The effects on these kinetics of a joint administration of Papaverine are considered.
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A pharmacokinetic study of 3H-labelled 7-rhamnoglycoside of 5,7,3'-trihydroxy-4'-methoxyflavone (3H-diosmine) administered both i.v. and orally, shows the great ease with which it is absorbed in digestion. A very sharp difference in elimination between the two modes of treatment must be associated with a difference in metabolism. A study of fixation confirms this conclusion. In particular the fixation on the tunica vascularis, perhaps due to a metabolite, appears relatively late. Furthermore the existence of an enterohepatic cycle assures a permanent hepatic binding.
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The pharmacokinetics of Cyclosporine A (CsA) was studied in male Wistar rats weighting 300 +/- 50 g trained to a 12:12 light-dark cycle. Oral administration (40 mg/kg) was performed at 1 of 4 different temporal stages: 09.00 h, 15.00 h, 21.00 h or 03.00 h (local time) i.e. 0200, 0800, 1400 or 2000 HALO (hours after light on). Blood samples were collected over 72-96 h after dosing, plasma was separated by centrifugation at 37 degrees C and stored frozen until assay, using radioimmunoassay (RIA). Two experiments were performed: the first with 4 groups of 48 rats and a non-specific polyclonal antibody (P-RIA); and the second with only 2 groups of 48 rats and a more specific monoclonal antibody (M-RIA). Plasma concentration data were evaluated with model-based linear pharmacokinetic concepts, with apparent zero-order or first-order absorption and n-exponential disposition (n = 1, 2 or 3): models MN0 or MN1. A compartment-independent approach was also conducted and led to area under the plasma concentration-time curve (AUC) and mean residence time (MRT) determinations. A comparison of the pharmacokinetic profiles across time of administration indicates that absorption, first-pass metabolism and tissue distribution of CsA in the rat are circadian-dosing stage dependent.
The pharmacokinetics of misonidazole, a hypoxic-cell radiosensitizer, were determinated after intraperitoneal administration to standardized Balb/c mice. The experimental data was fitted, using non linear analysis, to plasma-concentration curves described by tri-exponential equations derived from a two-compartment model. The pharmacokinetic constants (absorption and elimination coefficients) were determinated.
A two-compartment model with time delay is proposed to describe the pharmacokinetics of drugs subject to enterohepatic circulation. This model is applicable when the reabsorption is repeated several times at unequal intervals. Sample applications are provided.
Methotrexate (MTX), an effective agent in treatment of cancer, is one of the most versatile antineoplastic agents in spite of severe toxicity problems. The purpose of this study was to determine the circadian variation of this toxicity in order to decrease the side effects. The experiments were done in mice given a single i.p. dose. The toxicity of MTX, estimated from the relative weight loss, varied according to the time of administration, with a maximum after administration at 0900 (02 HALO). The dose-effect relationship can be described by a linear function: delta P/P versus log (dose). The slope of this line varies with the time of administration. These variations are correlated with the variations in biochemical [dihydrofolate reductase (DHFR) activity] and pharmacokinetic parameters (AUC) studied in previous works.