Pharmacokinetics of vancomycin in patients with various degrees of renal function

The pharmacokinetics of vancomycin were characterized in 56 patients with different degrees of renal function after an intravenous dose of 18.4 ± 4.7 mg kg-1 (mean ± standard deviation). Seven subjects had a creatinine clearance (CL(CR)) of >60 ml min-1 (group I), 13 had a CL(CR) of 10 to 60 ml min-1 (group II), and 36 had a CL(CR) of <10 ml min-1 (group III). Serial serum samples (range, 3 to 8) were collected during the 168 h after drug administration. The serum concentration-time profile in all patients demonstrated monoexponential decay. The mean half-lives were 9.1, 32.3, and 146.7 h in groups I, II, and III, respectively. A significant decline in serum clearance (CL(S)) was also noted (62.7 to 28.3 to 4.87 ml min-1 in groups I, II, and III, respectively). The steady-state volume of distribution varied from 0.72 to 0.90 liter kg-1. There was no significant relationship between the steady-state volume of distribution and CL(CR). The observed relationship between CL(S) and CL(CR) (CL(S) = 3.66 + 0.689 CL(CR); r = 0.8807) can be utilized to devise dosage schedules for patients with any degree of renal impairment. The relationship was utilized to develop a nomogram for initial and maintenance dosing of vancomycin.