Correlation between nephrotoxicity and pharmacokinetic parameters of gentamicin.
Gentamicin pharmacokinetics were determined in 26 critically ill adult patients. All had normal or only moderately reduced renal function based on serum creatinine concentration and clearance. The average half-life of elimination was 4.68 h, creatinine clearance was 3.9 l/h, and gentamicin clearance was 2.86 l/h. There was a highly significant correlation between the area under the serum concentration-time curves (AUC) and the peak and trough concentrations (r = 0.908, 0.980, P < 0.05, respectively). Serum gentamicin concentrations rose rapidly in 10 patients who showed deterioration of kidney function after 5 days of therapy. Gentamicin peak concentrations increased by 31%, while trough concentration increased by 121%. The mean percentage change in half-life was 68.49%, while the mean percentage change in renal function was 44.38%. Linear regression analysis of AUC versus the percentage change in kidney function revealed a significant increase in AUC with decrease in kidney function (r = 0.909, P < 0.05). There was a significant increase in half-life with decrease in kidney function (r = 0.948, P < 0.05).
el-Sayed
Y M
YM
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D005839:Gentamicins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D005839:Gentamicins; D003404:Creatinine