title: Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration.
abstract: Phenobarbital is the drug of choice for control of canine epilepsy. Phenobarbital induces hepatic enzyme activity, can be hepatotoxic, and decreases serum thyroxine (T4) concentrations in some dogs. The duration of liver enzyme induction and T4 concentration decreases after discontinuation of phenobarbital is unknown. The purpose of this study was to characterize the changes in serum total T4 (TT4), free T4 (FT4), thyroid-stimulating hormone (TSH), cholesterol and albumin concentrations, and activities in serum of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) after discontinuation of long-term phenobarbital administration in normal dogs. Twelve normal dogs were administered phenobarbital at a dosage of approximately 4.4-6.6 mg/kg PO q12h for 27 weeks. Blood was collected for analysis before and after 27 weeks of phenobarbital administration and then weekly for 10 weeks after discontinuation of the drug. The dogs were clinically normal throughout the study period. Serum ALT and ALP activity and TSH and cholesterol concentrations were significantly higher than baseline at week 27. Serum T4 and FT4 were significantly lower. Serum albumin and GGT were not changed from baseline at week 27. Changes in estimate of thyroid function (TT4, FT4, TSH) persisted for 1-4 weeks after discontinuation of phenobarbital, whereas changes in hepatic enzyme activity (ALT, ALP) and cholesterol concentration resolved in 3-5 weeks. To avoid false positive results, it is recommended that thyroid testing be performed at least 4 weeks after discontinuation of phenobarbital administration. Elevated serum activity of hepatic enzymes 6-8 weeks after discontinuation of phenobarbital may indicate hepatic disease.
authors.affiliation: Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Gieger
authors.forename: G
authors.initials: G
authors.lastname: Hosgood
authors.forename: J
authors.initials: J
authors.lastname: Taboada
authors.forename: K J
authors.initials: KJ
authors.lastname: Wolfsheimer
authors.forename: P B
authors.initials: PB
authors.lastname: Mueller
mesh_terms: D000304:Adrenal Cortex Function Tests / Q000662:veterinary; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D004283:Dog Diseases / Q000188:drug therapy; D004285:Dogs / Q000097:blood / Q000502:physiology*; D004827:Epilepsy / Q000188:drug therapy / Q000662:veterinary; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008111:Liver Function Tests / Q000662:veterinary; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology* / Q000627:therapeutic use; D012016:Reference Values; D013960:Thyroid Function Tests / Q000662:veterinary; D013961:Thyroid Gland / Q000187:drug effects* / Q000502:physiology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
chemical_list: D000927:Anticonvulsants; D013972:Thyrotropin; D002784:Cholesterol; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D013974:Thyroxine; D010634:Phenobarbital