Ethambutol kinetics in patients with impaired renal function

The pharmacokinetics of ethambutol (EMB) were investigated in 13 hospitalized patients with varying degrees of compromised renal function. Each patient was administered 15 mg/kg EMB by a constant-rate, 1-h infusion. Plasma and urine samples were collected for as long as 24 and 96 h, respectively, for analysis of EMB by electron capture gas-liquid chromatography. Plasma EMB concentrations appeared to decline multi-exponentially, with a terminal phase half-life of 7.4 to 11.8 h. Total body clearance of EMB ranged from 2.0 to 9.6 ml/min/kg and the steady-state volume of distribution from 0.80 to 3.60 L/kg. The fraction of EMB dose excreted unchanged in the urine varied from 0.03 to 0.26, and renal clearance varied from 0.07 to 0.57 ml/min/kg. The results of this study clearly indicate that renal failure decreases total body clearance and renal clearance and prolongs elimination half-life of EMB when compared with that in normal volunteers. The terminal phase elimination rate constant correlated significantly with creatinine clearance and the reciprocal of serum creatinine (y = 0.037 X +0.060, r = 0.795, p less than 0.05; y = 0.042 X +0.061, r = 0.783, p less than 0.05, respectively). Either creatinine clearance or serum creatinine of an individual patient would thus serve as a useful predictor for his or her capacity to eliminate EMB. Dosage adjustment is mandatory for EMB in patients with compromised renal function in order to achieve optimal therapy and to avoid undesirable side effects.