Effect of unilateral nephrectomy on the pharmacokinetics of amikacin in humans.
As unilateral nephrectomy is not a rare surgical procedure, it gives rise to the question whether drugs predominantly eliminated through the urinary tract can be handled effectively by the remaining kidney. Amikacin is predominantly excreted via glomerular filtration with only a small fraction undergoing tubular reabsorption, and can be used as a model drug of glomerular elimination. The study was carried out in 28 subjects, 10 one month and 10 one year after unilateral nephrectomy, as well as in 8 healthy subjects. The pharmacokinetics of amikacin was investigated after a 1-h infusion of 5 mg kg(-1) amikacin. Blood samples were collected for 24 h after the end of infusion. Pharmacokinetic parameters of amikacin were calculated using a one-compartment open model for intravenous administration. Amikacin concentrations were significantly elevated in nephrectomized patients as compared with control subjects, both 1 month and 1 year after the surgery, and were similar at these two time-points following unilateral nephrectomy. Pharmacokinetic parameters of amikacin in patients subjected to unilateral nephrectomy were significantly different from those observed in the control subjects. As compared with the controls, an increase in AUC (area under the serum concentration-time curve) by 81% (P < 0.001) and 63% (P < 0.01) 1 month and 1 year after nephrectomy was observed, respectively. The lambda(z) (elimination rate constant) was reduced by 39% (P < 0.001) after 1 month and by 38% (P < 0.001) 1 year after the operation and t 1/2 was prolonged by 70% (P < 0.001) and by 43% (P < 0.01) at the respective time-points following unilateral nephrectomy. CLT (total body clearance of the drug from plasma) and CL(BW) (clearance per kg body weight) were both significantly decreased in unilaterally nephrectomized subjects in comparison with the controls. CLT and CL(BW) were reduced by 53% (P < 0.001) and 42% (P < 0.01) 1 month after nephrectomy, and by 45% (P<0.001) and 42% (P<0.01) 1 year after the surgery, respectively. No significant differences among studied groups were found in C0 (initial serum drug concentration) and Vd (apparent volume of distribution). The results suggest that unilateral nephrectomy impairs elimination of amikacin, and possibly other drugs predominantly eliminated via glomerular filtration.
Drozdzik
M
M
Department of Pharmacology, Pomeranian Academy of Medicine, Szczecin, Poland. drozdzik@sci.pam.szczecin.pl
Domanski
L
L
Wojcicki
J
J
Gawronska-Szklarz
B
B
Machoy
P
P
Pudlo
A
A
D000328:Adult; D000583:Amikacin / Q000097:blood / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009392:Nephrectomy; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D000583:Amikacin; D003404:Creatinine