Gentamicin pharmacokinetics in diabetic dogs

Area of Science:

• Pharmacology
• Endocrinology
• Veterinary Medicine

Background:

• The terminal elimination phase of gentamicin, an antibiotic, is typically prolonged.
• Diabetes mellitus is a metabolic disorder that can affect drug pharmacokinetics.

Purpose of the Study:

• To investigate the impact of diabetes mellitus on gentamicin's elimination phase in dogs.
• To determine if diabetes mellitus alters gentamicin pharmacokinetics, irrespective of the diabetes model.

Main Methods:

• Compared gentamicin pharmacokinetics in normal dogs versus dogs with alloxan-induced or naturally occurring diabetes mellitus.
• Administered a standard dose of gentamicin intravenously to all study groups.
• Analyzed serum gentamicin concentrations over 7 days using non-compartmental pharmacokinetic methods.

Main Results:

• Gentamicin pharmacokinetics during the initial 8 hours were similar between normal and diabetic dogs.
• Diabetic dogs exhibited a significantly shorter mean residence time (MRT) for gentamicin compared to normal dogs.
• Clearance (Cls) was significantly greater, and volume of distribution at steady state (Vd(ss)) was significantly smaller in diabetic dogs.
• Serum gentamicin concentrations fell below 0.020 microgram/ml within 2 days in diabetic dogs, versus 0.048 microgram/ml at 7 days in normal dogs.

Conclusions:

• Diabetes mellitus, regardless of its cause (alloxan-induced or natural), abolishes the terminal elimination phase of gentamicin in dogs.
• This suggests that diabetes significantly alters gentamicin disposition, leading to faster clearance and reduced distribution.