Laboratory Evaluation and Serum Level of Phenobarbital Administered by Different Pathways in Dogs

Resumo

Background: Anticonvulsants are widely used in the treatment of small animals for the remission of isolated seizures and recurrent seizures in epilepsy, including tonic-clonic seizures and in status epileticus. Phenobarbital is the drug of choice for the management of epileptic seizures, it is considered very effective, safe, low cost and with few side effects. Several routes of administration may be used, with the oral, intravenous and intramuscular routes being the most common, with rectal and nasal routes being the least common.

 Materials, Methods & Results: Twenty mongrel dogs were used in the present study (aged 1 to 6-year-old, males and females, weighing 6.0 to 17.0 kg). The patients were previously evaluated via physical examination, temperature, respiratory and heart rate, laboratory tests (erythrogram and leukogram), and serum biochemistry by analyzing the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (FA), and gamma-glutamyltransferase (GGT). Four experimental groups were established with five animals in each group: animals receiving intramuscular injections of phenobarbital (VIM), animals receiving nasal administration of phenobarbital (VN), animals receiving rectal administration of phenobarbital (VR), and animals receiving oral administration of phenobarbital (VO). Phenobarbital was administered every 12 h for 15 days. To determine the serum level of phenobarbital, 5 mL of jugular vein blood was collected in vacuum tubes for evaluation via hemogram. The serum level was determined after 15 days of continuous administration of phenobarbital, as stable phenobarbital serum levels can only be achieved from 10 to 15 days after the first administration. For the serum biochemistry evaluation, 10 mL of blood from the jugular vein was collected using vacuum syringes for assessing ALT, AST, GGT, and FA levels. Statistical analyses were performed with contrasted variation analysis using the Tukey method and paired t-test for comparison of time points. The level of significance was determined to be 5%. There was a significant difference (P < 0.05) among drug administration routes, and among the levels of AST and AF enzymes after the first administration of phenobarbital via the nasal and intramuscular routes. Based on the results, it was concluded that hepatic alterations secondary to the use of phenobarbital for 15 days may occur with a low incidence. The phenobarbital serum concentration in dogs varied when administered via nasal, rectal, and intramuscular routes, but was stable when administered orally.

Discussion: The current results are consistent with those of previous studies, indicating that the chronic use of phenobarbital causes an increase in the serum levels of ALT and FA enzymes. It was found that phenobarbital serum levels varied greatly, particularly following nasal, rectal, and intramuscular administration. In the present study, serum phenobarbital levels were within the normal range when administered via the intramuscular, nasal, rectal, and oral routes. This result is inconsistent with that of previous studies where the serum levels were below the normal range following oral administration of phenobarbital. The serum concentration, rather than clinical criteria, should be used as a guide for treatment modification, as the distribution of this drug varies greatly among animals.