Gentamicin pharmacokinetics in diabetic dogs

S. A. Brown, Richard W Nelson, C. Scott-Moncrieff

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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 non-compartmental 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, Cl(s) was greater (3.01 ± 0.86 ml/min/kg) than in normal dogs (1.45 ± 0.11 ml/min/kg; P < 0.01), whereas V(d(ss)) was smaller in diabetic dogs (0.405 ± 0.508 l/kg) than in normal dogs (8.56 ± 4.48 l/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.

Original languageEnglish (US)
Pages (from-to)90-95
Number of pages6
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume14
Issue number1
StatePublished - 1991
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

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