A pharmacokinetic study of phenobarbital in mature horses after oral dosing

Abstract

The pharmacokinetics of phenobarbital were determined in six mature horses after a single oral dose. Horses were administered a 5.5 mg/kg of body weight oral dose of phenobarbital tablets. Based on the combined evaluation of i.v. and oral results, phenobarbital displayed two-compartment pharmacokinetics in the horse with a terminal half-life of 19.0 +/- 4.4 (mean +/- SD) h. This half-life is considerably shorter than those reported for dogs and humans. The steady-state volume of distribution (Vdss/F) and the total body clearance (Clt/F) of phenobarbital were 0.753 +/- 0.115 l/kg and 27.9 +/- 9.2 ml/h/kg, respectively. The average extent of oral absorption was 101% with a range of 76 to 124% among the six horses. Examination of the absorption kinetics demonstrated a biphasic absorption process in four horses with a rapid absorption followed by a slower absorption phase. The mean residence time (MRT) was 36.9 +/- 4.1 h and the mean residence time for oral absorption (MRTabs) was 11.3 h. Based on the results of the present study, an oral dosing regimen of 11 mg/kg of body weight every 24 h can be recommended.

Differential Diagnosis and Management of Horses with Seizures or Alterations in Consciousness

“…22 Phenobarbital is well absorbed after oral administration, with a bioavailability close to 100% in horses. 23 The majority of the drug is metabolized in the liver, with approximately 25% excreted as unchanged drug in horses. 8 Phenobarbital induces the hepatic cytochrome P450 enzyme complex, resulting in a more rapid metabolism not only of phenobarbital but also of other concurrently administered drugs.…”

“…[23][24][25][26] The goal of any antiepileptic therapy is to achieve a therapeutic steady-state condition, which is usually reached within five to six elimination half-lives. Given the variability in half-life, clearance, and metabolism of phenobarbital, as noted above, therapeutic monitoring is necessary to ensure that adequate anticonvulsant concentrations are obtained, and toxicity avoided.…”

“…7,21,30 period), followed by maintenance doses of 9 mg/kg IVq 8 h. 26 In adult horses, a parenteral loading dose of 12 mg/kg IV, followed by 6.65 mg/kg IV (20 min infusion) q 12 h, 25 is adequate to reach appropriate therapeutic concentrations. Maintenance therapy is usually administered by the oral route, with a proposed dose of 11 mg/kg once q 24 h in adults, 23 although the half-life of phenobarbital is unknown after oral maintenance therapy in foals. Overall, phenobarbital is well tolerated in horses.…”

Bioavailability and pharmacokinetics of sulfamethazine in the pony

“…and oral data, and the estimates for the absorption rate and time lag to absorption (tpag) were found by the simultaneous fitting of ' oral and i.v. data (Ravis et al, 1987). Mean resident times for i.v.…”

“…Mean resident times for i.v. administration (MRT) and for absorption (MRTabs), were calculated as previously described (Ravis et al, 1987). All data are reported as the mean f SD except for the tIj2* which are harmonic means (Miller,197kj.…”