Influence of thyroid function on the pharmacokinetics of gentamicin in pigs

Hypothyroidism or hyperthyroidism was induced in 10 pigs (5 pigs/group) and each pig was administered gentamicin (6 mg/kg of body weight, IV). Low thyroxine and triiodothyronine resulted in a decrease in creatinine clearance (P = 0.04), an increase in serum creatinine concentration (P = 0.003), and a decrease in gentamicin systemic clearance (P = 0.002), compared with findings in control pigs (n = 5). These effects probably were secondary to a decreased glomerular filtration rate associated with hypothyroidism. A strong correlation among the 3 treatment groups was found between gentamicin systemic clearance and creatinine clearance (r = 0.72; P = 0.004) and between gentamicin systemic clearance and serum creatinine concentration (r = -0.77; P = 0.0007). Hyperthyroidism induced a slight but significant decrease in protein binding (P = 0.002). However, the significant changes in the hypothyroid pigs and the hyperthyroid pigs were not of a magnitude sufficient to alter gentamicin elimination half-life. Gentamicin disposition was best described, with a 4-compartment open model.