Pharmacokinetics of the novel anticonvulsant hepp after single intravenous administration of three different doses in dogs

✍ Scribed by Lisbeth E. Gómez M.; Pedro A. Lehmann F.

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 385 KB
• Volume: 16
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510160205

✦ Synopsis

HEPP (D, L-3-hydroxy-3-ethyl-3-phenylpropanamide) is a novel compound with a wide spectrum of anticonvulsant activity and relatively low toxicity. The aim of this investigation was to study the pharmacokinetics of HEPP in mongrel dogs and to assess its linearity after intravenous administration of 8, 15, and 30mg kgg'. A biphasic disappearance pattern with a rapid distribution phase was observed in the plasma concentration versus time curve. The mean terminal half-life (t,,,& was the same after the three doses (3.4k0.15 h) and the mean half-lives of the distribution phase were not significantly different after the three doses (0-09+0-02, 0-08 fO.07, and 0.11 & 0-03 h for 8, 15, and 30 mg kg-' respectively). The mean AUC,-, values were 44.1&10.8, 72.1&8.8, and 127.4f23.2pghmLg1, respectively, showing a linear increase. The individual values of AUC,-, corrected for the administered dose (AUC,-,/D) were 0-29+0.04,0*23+0.05, and 0.22&0.06hmL-'. These values were not statistically different. Neither the mean residence time (MRT = 4.55 & 1 50, 4 * 9 0 & 1.32, and 5 -0 7 ? 1.95 h), the steady state volume of distribution (Vs,=0.86f0-1l, 1-01f0-17, and 1.20+0.4OLkg-') nor the systemic clearance (Cl=3-36+0-82, 3-53f0-44, and 4.02&0.68mLmin-' kg-') showed significant differences between doses. The values of V,, suggest that HEPP is distributed in the whole body fluid. The invariant pharmacokinetic parameters and the direct correlation between AUC,_, and the dose suggest that the kinetics of HEPP in dogs are linear over the range of doses studied.