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.
D000704:Analysis of Variance; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005839:Gentamicins / Q000378:metabolism* / Q000633:toxicity; D006207:Half-Life; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects; D007700:Kinetics; D011485:Protein Binding; D011897:Random Allocation; D012044:Regression Analysis; D013552:Swine; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D005839:Gentamicins; D014284:Triiodothyronine; D003404:Creatinine; D013974:Thyroxine