An indirect method for absorption rate estimation: Flurothyl-induced seizures
- 127 Downloads
This paper develops a method to estimate a minimal amount of flurothyl necessary to induce the seizures (the seizure threshold). A simple mathematical model is proposed which permits one to determine the drug absorption rate from the amount which has been administered and from the measured latency to onset of seizure. Experimental animal (rats) were exposed to a continuous intake of flurothyl in two different situations: either being alone in the airtight chamber or sharing it in a pair. In the latter case, we assume that the two rats uniformly share the infused drug. Our calculations estimate that approximately 20 μl of flurothyl is necessary to induced twitches, whereas 25 μl of flurothyl is the dose required for the induction of clonic seizures. The model can be used to estimate the threshold amounts of any drug producing obvious behavioral changes irrespective of the route of administration.
KeywordsStatus Epilepticus Absorption Rate Seizure Type Clonic Seizure Seizure Threshold
Unable to display preview. Download preview PDF.
- Holmes, G. L. 1991. The long-term effects of seizures on the developing brain: clinical and laboratory issues.Brain Dev. 13, 393–409.Google Scholar
- Prichard, J. W., B. B. Gallagher and G. H. Glase. 1969 Experimental seizure threshold testing with flurothyl.J. Pharm. Exp. Ther. 166, 170–178.Google Scholar
- Ricciardi, L. M. and S. Sato. 1990. Diffusion processes and first-passage-time problems. InLectures in Applied Malthematics and Informatics, L. M. Ricciardi (Ed.) Manchester: Manchester University Press.Google Scholar
- Terndrup, T., F. Starr and W. E. Fordyce. 1994. A piglet model of status epilepticus: comparison of cardiorespiratory and metabolic changes with two methods of pentylenetetrazol administration.Ann. Emerg. Med. 23, 470–479.Google Scholar
- Tortella, F. C., L. Robles, J. M. Witkin and A. H. Newman. 1994. Novel anticonvulsant analogs of dextromethorphan: improved efficacy, potency, duration and side-effect profile.J. Pharmacol. Exp. ther. 268, 727–733.Google Scholar
- Truitt, E. B., E. M. Ebesberg and A. S. G. Ling. 1960. Measurement of brain excitability by use of hexaflurodiethyl ether (Indoclon).J. Pharm. Exp. Ther. 129, 445–453.Google Scholar
- Weiss, M. 1991. Residence time distribution in pharmacokinetics: behavioral and structural models. InAdvanced Methods in Pharmacokinetic and Pharmacodynamic Systems Analysis, D. Z. D'Argenio (Ed), pp. 89–101. New York: Plenum Press.Google Scholar
- Young, R. S., O. A. Petroff, B. Chen, J. C. Gore and W. J. Aquila. 1991. Brain energy state and lactate metabolism during status epilepticus in the neonatal dog: in vivo 31P and 1H nuclear magnetic resonance study.Pediatr. Res. 29, 191–195.Google Scholar
- Zhong, J., O. A. Petroff, J. W. Prichard and J. C. Gore. 1995. Barbiturate-reversible reduction of water diffusion coefficient in flurothyl-induced status epilepticus in rats.Magn. Reson. Med. 33, 253–256.Google Scholar
- Zis, A. P., G. G. Nomikos, E. E. Brown, G. Damsma and H. C. Fibiger. 1992. Neutrochemical effects of electrically and chemically induced seizures: an in vivo microdialysis study in the rat hippocampus.Neuropsychopharmacology 7, 189–195.Google Scholar