Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of baclofen in mice

被引：0
作者：
Graciela N. Balerio
Modesto C. Rubio
机构：
[1] Universidad de Buenos Aires,Cátedra de Farmacología, Facultad de Farmacia y Bioquímica
[2] Instituto de Investigaciones Farmacológicas,undefined
来源：
European Journal of Drug Metabolism and Pharmacokinetics | 2002年 / 27卷
关键词：
Pharmacokinetic; Pharmacodynamic modeling; baclofen; antinociceptive effect; mice;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The aim of this study was the development of a pharmacokinetic-pharmacodynamic (PK/PD) model of the antinociceptive effect of baclofen in mice. We studied the dose response curve of the analgesic action of baclofen in mice by hot plate test. Baclofen produced a dose dependent antinociceptive effect with doses between 1–3 mg/kg administered intraperitoneally (i.p.) (ED50: 1.94 mg/kg of racemate) and this effect fits to a linear pharmacodynamic model. Blood and brain concentrations of (−)3H-baclofen were determined by Thin-Layer Chromatography (TLC) and counted in the scintillation-counter. The PK/PD models were analyzed with the PC-TOPFIT V.2.0 and the tests for distinguishing between models were several adjustment parameters as Akaike information criterion (AIC), Imbimbo criterion (Ip), standard desviation (SD) and the correlation coefficient (r2). Accordingly with these adjustment parameters, a 2 compartment open model was selected where plasma is the central compartment and brain is in the peripheral compartment. In this model, the effect is linked to the peripheral compartment.
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页码：163 / 169
页数：6
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  • [1] DeFeudis F.V.(1977)GABA receptors in the vertebrate nervous system Prog. Neurobiol. 9 123-145
  • [2] Hösli L.(1978)Action and uptake of neurotransmitters in CNS tissue culture Rev. Physiol. Biochem. Pharmac. 81 135-188
  • [3] Hösli E.(1978)Neuropharmacology of aminoacid inhibitory transmitters Ann. Rev. Pharmacol. Toxicol. 18 269-289
  • [4] Johnston G.A.R.(1982)GABA-ergic analgesia-a naloxone insensitive system Pharmac. Res. Commun. 14 383-390
  • [5] DeFeudis F.V.(1984)GABA-ergic mechanisms in antinociception. Prog. Neuropsychopharmac Biol. Psychiat. 8 581-586
  • [6] Sawynok J.(1985)Minireview, GABA in morphine analgesia and tolerance Life Sci. 37 199-208
  • [7] Sivam S.P.(1980)(−)-Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor Nature 283 92-94
  • [8] Ho I.K.(1987)Baclofen induces catatonia in rats Neuropharmacology 26 1419-1423
  • [9] Bowery N.G.(1987)Hypothermia induced by baclofen, a possible index of GABAB receptor function in mice, is enhaced by antidepressant drugs and ECS Brit. J. Pharmacol. 92 863-870
  • [10] Hill D.R.(1990)Effect of baclofen, a GABAB agonist on forced swimming-induced immobility in mice Arch. Int. Pharmacodyn. 307 18-31
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