EFFECTS OF DIETARY-PROTEIN CONDITIONING ON GENTAMICIN PHARMACOKINETICS IN DOGS

Eighteen, six-month-old male Beagles with normal renal function were r andomly 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 termin al 2 day testing period), gentamicin was administered at a dosage of 1 0 mg/kg q. 8 h for 8 days. The first dose on days 1 and 7 was administ ered i.v. and all others were given i.m. Pharmacokinetic parameters we re determined using blood samples collected over an 8 h period followi ng the i.v. dose on day 1. The elimination rate constant was calculate d 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 clear ance greater in the high protein group compared to the other two group s. No difference was found in the rate of elimination between days 1 a nd 7 for the high protein group; however, in the medium and low protei n groups the rate of elimination decreased over the 7 days of treatmen t. Therefore, high dietary protein prior to and during gent-amicin adm inistration induced faster gentamicin clearance and a larger volume of distribution and preserved the ability to eliminate gentamicin in dog s with normal renal function.