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Pharmacokinetics of orally administered phenobarbital in African grey parrots (Psittacus erithacus erithacus).

Phenobarbital is currently the most frequently prescribed anticonvulsant in small animal medicine, primarily because of its efficacy, long half-life, low expense and safety. Phenobarbital is an anticonvulsant barbiturate, which inhibits seizures at doses lower than those that produce anaesthesia. It is effective as an anticonvulsant in part because of its potentiating action on the inhibitory neurotransmitter gamma aminobutyric acid, which increases the seizure threshold and lowers the electrical activity of the seizure focus. As summarized in reviews, phenobarbital has high oral bioavailability in domestic animals (Vernau & LeCouteur, 2002; Papich, 2009). The drug is highly metabolized via hepatic cytochrome P450 enzymes (Hojo et al., 2002; Vernau & LeCouteur, 2002; Papich, 2009). In dogs, phenobarbital also induces plasma a1-acid glycoprotein, which is the main plasma binding protein for basic drugs (Hojo et al., 2002). The elimination half-life of phenobarbital in humans, dogs and cats has been reported to be 70–100, 37–75 and 35–76 h, respectively. Because of the variability in pharmacokinetics among individuals, therapeutic drug monitoring is recommended to optimize the individual patient dosage (Papich, 2009). Although oral phenobarbital has been investigated in pigeons for the response to external discriminative stimulus (Picker and Poling, 1984; Picker et al., 1986; White et al., 1994), no studies have been reported on the anticonvulsant effects of phenobarbital in birds. The Congo African grey parrot (Psittacus erithacus erithacus) is a popular companion bird, and seizures have been associated with several diseases in this species, including hydrocephalus and hypocalcemia (McDonald, 1988; Fleming et al., 2003; Steinmetz et al., 2008). Because information on pharmacokinetics of phenobarbital in parrots has not been studied, there is no guidance for dosage regimens. This investigation was performed to examine the pharmacokinetics of orally administered phenobarbital in African grey parrots. There was only a small population available (a total of six birds) for study. The total volume of blood that could be harvested from an individual bird for each trial was no more than approximately 4–5 mL, limiting the number of blood draws possible because of the minimum plasma volume requirement for drug assay. Therefore, our objective was to present this as a preliminary report that can potentially serve as a basis for further study. Five privately owned Congo African grey parrots of mixed gender ranging in age from 4 to 22 years and in weight from 0.381 to 0.536 kg on varied diets that had never previously received phenobarbital were determined to be in good health based on physical examination, haematology and plasma biochemistries. Birds were allowed to drink and feed ad libitum during the study period. Phenobarbital solution was extemporaneously prepared using modifications from a previous report (Cober & Johnson, 2007). A 30 mg ⁄ mL solution was prepared by crushing 64.8-mg tablets and mixing with equal portions of Ora-Plus and Ora-Sweet (Paddock Laboratories, Minneapolis, MN, USA). Birds were administered a single oral dose of 17 mg ⁄ kg phenobarbital directly per os (PO). The dosage used was the highest dosage administered to a single sentinel African grey parrot with seizures of unknown cause without clinical response to phenobarbital administration and suboptimal plasma concentrations determined through periodic monitoring. Blood samples (0.40 mL ⁄ sample) were collected from the right jugular vein using a 25 g 5 ⁄ 8 inch needle on a 1-mL syringe prior to drug administration and at 1, 2, 4, 6 and 8 h after drug administration. After collection, blood samples were placed into tubes coated with lithium heparin (BD Microtainer, Franklin Lakes, NJ, USA). Samples were immediately centrifuged (12 000 g) for 90 sec and the plasma decanted and delivered on ice to the laboratory within 24 h for processing. Because of the high degree of variability in plasma concentrations of phenobarbital among birds in the first trial, a second trial was performed with a solution, rather than a suspension with the goal of producing more consistent oral absorption with the drug dissolved in the formulation. Four of the five birds in the second trial had been used in the first trial, with a ten-week wash-out period in between trials. In the second trial, a solution was extemporaneously prepared by combining 1 mL of injectable phenobarbital solution (130 mg ⁄ mL; Baxter Healthcare Corp, Deerfield, IL, USA) with 12-mL glycerine for a final concentration of 10 mg ⁄ mL. Birds were fasted for 8 h or more prior to and during the drug trial, and were administered drug by intracrop gavage using a ball-tipped stainless steel feeding tube (GA). The feeding tube was flushed after drug delivery with J. vet. Pharmacol. Therap. 34, 615–617. doi: 10.1111/j.1365-2885.2011.01279.x. SHORT COMMUNICATION