Effects of dietary protein conditioning on gentamicin pharmacokinetics in dogs

Eighteen, six-month-old male Beagles with normal renal function were randomly divided into three groups of 6. Each group was fed a diet that was similar except for protein content (high = 26%, medium = 13% and low = 9%, all on an as fed basis) throughout the experimental period. After a 21 day dietary protein conditioning period (including a terminal 2 day testing period), gentamicin was administered at a dosage of 10 mg/kg q. 8 h for 8 days. The first dose on days 1 and 7 was administered i.v. and all others were given i.m. Pharmacokinetic parameters were determined using blood samples collected over an 8 h period following the i.v. dose on day 1. The elimination rate constant was calculated on days 1 and 7. The data best fit a two-compartment open model for all dogs on day 1. The volume of distribution was higher and the clearance greater in the high protein group compared to the other two groups. No difference was found in the rate of elimination between days 1 and 7 for the high protein group; however, in the medium and low protein groups the rate of elimination decreased over the 7 days of treatment. Therefore, high dietary protein prior to and during gentamicin administration induced faster gentamicin clearance and a larger volume of distribution and preserved the ability to eliminate gentamicin in dogs with normal renal function.