Effect of protein binding on cefmenoxime steady-state kinetics in critical patients

The effect of protein binding on cefmenoxime steady-state kinetics was studied in 20 critical patients with gram-negative pneumonia. Sixteen patients- were given I gm cefmenoxime ever. 6 hr, two received 2 gm eve ry 6 hr, and two received 2 gm every 8 hr. Serum protein binding was measured by equilibrium dialysis. Assays were by HPLC. Serum cefmenoxirne concentration-time data were characterized by a model-independent method based on statistical moment theory. Despite varying renal function in patients, mean cefmenoxime serum concentration-time curves joy- all three closing regimens were closely aligned, reflecting successful empiric dosage adjustment. Terminal phase t 1 2 ranged from 0.8 to 2.9 hr and was significantly related to creatinine clearance. Cefmenoxime total clearance was significantly related to both λ_z (2.303 times the slope of the terminal portion of the log-concentration-time curve) and creatinine clearance (CCr). Plasma clearance of free cefmenoxime was more strongly correlated with CCr than the clearance of total cefmenoxime. Drug recovery from 24-hr urine collections at steady state was 76.9 ± 19.8% of the daily dose (mean ± SD, n = 13). Cefmenoxime protein binding in patients differed markedly from normal values. A regression equation derived from data on 11 cephalosporins appeared to predict total volume of distribution in the steady state (Vd_ss-Total) from the fraction of unbound drug accurately. Since cefmenoxime has a high therapeutic index no clinical consequences are expected to result from variation in protein binding. Observed differences in protein binding between patients and normal subject.% could have clinical consequences joy highly bound acidic drugs that, unlike cefmenoxime, have narrow therapeutic indices.