Effects of urine pH modification on pharmacokinetics of phenobarbital in healthy dogs

Although pH modification is one of the effective strategies for dissolving or preventing uroliths, little is known about its effects on the pharmacokinetics of phenobarbital in dogs. Five spayed, female Beagles were fed with a twice-daily diet that included potassium citrate and ammonium chloride for urine alkalinization and acidification, respectively. After a stabilizing period of 7 days, a single clinical dose of phenobarbital (3 mg/kg) was orally administered, and time-course changes in its serum and urine concentrations were determined by high-performance liquid chromatography. Total amounts of unchanged phenobarbital excreted into urine for 216 h were decreased by urine acidification and increased by urine alkalinization. The elimination half-life of serum phenobarbital in dogs with urine alkalinization was shortened and ClR increased when compared with dogs with urine acidification. Other pharmacokinetic parameters, including Cmax, Tmax, AUC₀₋₂₁₆, Cl/F, and Ae₀₋₂₁₆ were not changed by modification of the urine pH. These results suggest that the pH of urine is likely to be a determinant of the pharmacokinetics, especially urine excretion rate, of a clinical dose of oral phenobarbital. It is possible that the serum concentration of phenobarbital might be altered when a pH modifying-diet is administered for the purpose of dissolving or preventing uroliths.