[Effects of cyclic 3'5' AMP on the development of pancreatic islands of Langerhans].
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Biomedical subjects
Publications and source records attributed to R Alric.
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The pharmacokinetics of apyramide, an ester of indomethacin and acetaminophen (paracetamol), were determined after intravenous administration to nine beagle dogs. Indomethacin and its pro-drug, apyramide, were extracted from acetonitrile-precipitated plasma by a solvent-demixing procedure and the concentration of these two drugs was measured by a reversed-phase liquid chromatographic assay. The kinetic evolution with time of plasma levels of apyramide and of indomethacin resulting from enzymatic hydrolysis was compared with values obtained for indomethacin injected in equimolar dose. Plasma levels of apyramide quickly decreased and the mean (+/- SD) half life was 0.15 +/- 0.08 h. For metabolic indomethacin, the mean (+/- SD) area under curve was 12.36 +/- 4.80 mg.h/l and the mean (+/- SD) half life of terminal phase was 16.71 +/- 9.46 h. After administration of indomethacin, these values were 17.60 +/- 4.12 mg.h/l and 7.89 +/- 2.20 h, respectively.
The pharmacokinetics of sodium thiopental was studied in 9 normal dogs of various ages by the usual bolus method. Data were fittable by a two compartment open model in 8, three compartments were needed in one. Constant-rate infusions, as used in cerebral resuscitation, were performed in 6 of them. As expected, constant blood levels could not be obtained during the distribution phase which lasted about 6 hours. From the individual pharmacokinetic constants, the time equation of infusion rate intended to exactly compensate for distribution was calculated. The resulting "modulated infusions" succeeded in reducing the blood level trough from 50% to 20%. After the end of infusions, the decrease of plasma levels exhibited a non linear pattern which had not been noticeable in the elimination phase after boluses. Such unknown non linearity may lead to systematic errors when calculating pharmacokinetic parameters: this could explain why a complete correction was not obtained with modulated infusions. A better parametrization method in the case of non-linear elimination is under study.
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