Gentamicin pharmacokinetics during slow daily home hemodialysis.

Abstract

Gentamicin is commonly used in hemodialysis patients. Gentamicin pharmacokinetics during traditional hemodialysis have been described. Slow daily home (SDH) hemodialysis (7 to 9 hours a day/6 days a week) use is increasing due to benefits observed with increased hemodialysis. We determined gentamicin pharmacokinetics for SDH hemodialysis patients. Eight patients (four male and four female) received a single intravenous dose of 0.6 mg/kg gentamicin post-hemodialysis. Blood samples were collected at 5, 10, 15, 30, and 60 minutes after dose. The next day patients underwent a typical SDH hemodialysis (high-flux F50NR dialyzer) session. Blood samples were taken at 0, 5, 15, 60, 120, 240, 360, 480 minutes during and 15, 30 and 60 minutes post-hemodialysis. Baseline and 24-hour urine samples were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. Patients were 42.5 +/- 13.1 years old (mean +/- SD). Inter-, intra-, and post-hemodialysis collection periods were 17.0 +/- 2.1 hours, 8.1 +/- 0.4 hours, and 1.1 +/- 0.1 hours, respectively. Intra-, and interdialytic gentamicin half-lives were different (intradialytic, 3.7 +/- 0.8 hours; interdialytic, 20.4 +/- 4.7 hours; P < 0.0001). Hemodialysis clearance accounted for 70.5% gentamicin total clearance. Renal clearance correlated with glomerular filtration rate (GFR) (renal clearance=1.2 GFR; r2=0.98; P < 0.001). Mean peak and trough of hemodialysis concentrations were 1.8 +/- 0.6 microg/mL and 0.5 +/- 0.2 microg/mL, respectively. Post-hemodialysis rebound was 3.1 +/- 8.8% at 1 hour. Pharmacokinetic model predicts 2.0 to 2.5 mg/kg dose gentamicin post-hemodialysis would provide peak (1 hour post-dose) and trough (end of SDH hemodialysis session) concentrations of 6.0 to 7.5 microg/mL and 0.7 to 0.8 microg/mL, respectively. This would provide adequate coverage for most gram-negative organisms in SDH hemodialysis patients.