Pharmacokinetics, effects on renal function, and potentiation of atracurium-induced neuromuscular blockade after administration of a high dose of gentamicin in isoflurane-anesthetized dogs

Abstract

Objective - To determine pharmacokinetics, renal effects, and effect on atracurium-induced neuromuscular blockade of a high dose of gentamicin in isoflurane-anesthetized dogs. Animals - 6 healthy, adult, mixed-breed dogs, anesthetized twice and receiving gentamicin (6 mg/kg of body weight, IV) or saline solution. Procedure - Blood samples were collected before and at intervals after gentamicin administration. Pharmacokinetic values were evaluated by use of multivariant stepwise linear regression analysis. Gentamicin-induced renal changes were assessed by comparing pretreatment and 12- to 24-hour posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-γ-glutamyl-transferase ratio, and urinalysis. Neuromuscular blockade, maintained by atracurium infusion, was assessed, using the train-of-four response. At stable 50% depression of first twitch (T1), gentamicin or saline solution was given. Before and at posttreatment intervals for 60 minutes, T1% and fourth twitch-to-T1 ratio were recorded. The infusion was discontinued and 50 to 75% T1 recovery time was recorded. At 75% T1, edrophonium (0.5 mg/kg) was administered IV. Results - Mean values for volume of distribution and clearance were 0.263 L/kg and 2.0 ml/min/kg, respectively. Mean maximal serum concentration of gentamicin was 46.4 μg/ml. Pre and posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-γ-glutamyltransferase ratio, and other urine analytes were not significantly different. Mean (∓ SD) values for T1% and fourth twitch-to-T1, ratio decreased significantly after gentamicin (depression was maximal at 5 minutes). Recovery time (50 to 75% T1) was not different between groups. Edrophonium restored twitch to baseline. Conclusions - Mean values for apparent volume of distribution and total body clearance of gentamicin were similar to values in unanesthetized dogs. Mean maximal serum concentration of gentamicin was greater than that in unanesthetized dogs. Renal function was unaffected. Gentamicin potentiated atracurium-induced neuromuscular blockade, but did not affect recovery time.