Gentamicin pharmacokinetics in diabetic dogs

Abstract

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, Five normal dogs, three dogs with alloxan‐induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using noncompartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days, MRT in normal dogs (5830 ± 2970 min, mean ± SD) was longer (P < 0.01) than in diabetic dogs (136 ± 164 min). In diabetic dogs, Cls was greater (3.01 ± 0.86 ml/min/kg) than in normal dogs (1.45 ± 0.11 ml/min/kg; P < 0.01), whereas Vd(ss) was smaller in diabetic dogs (0.405 ± 0.508 1/kg) than in normal dogs (8.56 ± 4.48 1/kg; p,<0.01). Serum gentamicin concentrations were less than 0.020 μg/ml by 2 days in all of the diabetic dogs, but were 0.048 ± 0.018 (μg/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non‐rodent species.

Effect of polyaspartic acid on pharmacokinetics of gentamicin after single intravenous dose in the dog

“…In contrast to the present study, in previous studies in which blood was sampled for 8 h or less or the detection limit of the assay used was greater than 0.1 g/ml, a twocompartment open model usually described the pharmacokinetics of gentamicin in plasma adequately (4). In this study, the pharmacokinetic parameters reported for the central and shallow compartments in control dogs are similar to those previously reported (3,14,15). A slow elimination phase of a threecompartment open model was very clearly demonstrated by Brown et al (3) with sample time points between 12 and 192 h postinjection.…”

“…The pharmacokinetics of gentamicin in the dog have been described previously. These reports describe data which satisfy either two-compartment (14,15) or three-compartment (3) open models. In contrast to the present study, in previous studies in which blood was sampled for 8 h or less or the detection limit of the assay used was greater than 0.1 g/ml, a twocompartment open model usually described the pharmacokinetics of gentamicin in plasma adequately (4).…”

Comparative pharmacokinetics of aminoglycoside antibiotics

“…The plasma elimination phase (p phase) is correlated well with GFR in the animal species (Sojka & Brown, 1986;Frazier et al, 1988); as $hewn in Table I, t,/p in normal animals range from 1 h in dogs Brown et al, 1991) and rabbits (Huang et ul., 1979), 1.25 h in cats (Short et al, 1986;Jernigan et al, 1988a), 1.35 h in hawks (Bird et al. 1983).…”

Pharmacokinetics of Gentamicin C 1 , C 1a , and C 2 in Beagles after a Single Intravenous Dose

“…The presence of a deep-compartment and a three-compartment model of gentamicin disposition was suggested (3,24,27), and in some studies a terminal half-life (t 1/2 ) of more than 100 h was observed (3,20,21). However, other reports concluded that a two-compartment model best described gentamicin pharmacokinetics and were unable to observe the deep compartment (6,17,18).…”