Cefmenoxime pharmacokinetics in healthy volunteers and subjects with renal insufficiency and on hemodialysis

Abstract

The pharmacokinetics of cefmenoxime were characterized in five healthy volunteers and in 15 subjects with various degrees of renal insufficiency after a single 10-mg/kg, 5-min intravenous infusion. Five of these subjects were studied both on hemodialysis and during an interdialytic period. Plasma, urine and dialysate were assayed for cefmenoxime by a specific high-pressure liquid chromatographic assay. Peak plasma concentrations of cefmenoxime were ca. 94 ,ug/ml after completion of the infusion. The mean plasma and renal clearances in the healthy volunteers were 281 ± 66 and 228 ± 52 ml/min, respectively. Plasma clearance declined in patients with renal insufficiency and correlated significantly with creatinine clearance. The mean apparent volume of distribution at steady state in the healthy volunteers was 0.23 liters/kg and was not found to be significantly different in subjects with renal insufficiency. The mean cumulative 24-h urinary recovery of cefmenoxime in healthy volunteers was 81 % of the administered dose and decreased with reduced renal function. Cefmenoxine dosage should be reduced in proportion to the decline in creatinine clearance. A simple nomogram for dose selection is provided.

Pharmacokinetics of cefmenoxime in patients with impaired renal function and in those undergoing hemodialysis

“…The serum cefmenoxime levels after intravenous administration were described in terms of a two-compartment open model, and the individual serum level profiles were fitted to a biexponential function of the form: C = A x e-a' + B x e-t, in which C is the concentration of antibiotic in serum at time t postdosing; a and 1 are the rate constants governing the distribution and elimination phases of drug loss from serum, respectively; and A and B are the intercepts of slopes a and P with the ordinate. Pharmacokinetic analysis was performed with a nonlinear least-squares program developed by Yamaoka et al (17) (7), although a somewhat longer tY2p, has been reported by others for healthy subjects (4,6,12,14). Thus, the t12, of cefmenoxime after intravenous dosing in subjects with normal renal function is comparable to that of cefotax- ime (0.9 to 1.2 h), but is shorter than those of other cephalosporins (1,8).…”

“…3). Thus, assuming that the standard individual dose schedule of cefmenoxime in subjects with normal renal function is 1.0 g intravenously every 6 h, the same standard individual dose may be given every 8 h for those with a CLCR of 60 ml/min per 1.73 m2, every 12 h for those with CLCR of 50 ml/min per 1.73 m2, and every 24 h for those with CLCR of 20 ml/min per 1.73 i2. Application of the same rule to those patients with severe renal failure would be rather inappropriate since it is expected to produce a drug level in-serum that is too low over a prolonged time.…”

Elimination of cefmenoxime during continuous haemofiltration

“…In 9 patients (1-9) the study was done after a single intravenous dose of 1 g CMX and in 3 patients (10-12) after repeated IV doses of 0.5 g b. d. Blood was obtained from the arterial line before and 2 min and 0.5, 1,2,4,8,12, and 24 h after bolus injection of CMX into the venous line of the haemofiltration system. Filtrate was collected over 12 or 24 h. Serum separated after centrifugation and filtrate were stored at -20 °C until analysed.…”

“…rain -1.1.73 m -2. The elimination half-life was 15.6 (7.5) h. During haemodialysis 16-51% of the administered dose was recovered in the dialysate (Gambertoglio et al 1984). No data are available about the elimination of CMX during continuous haemofiltration.…”

Guide to Drug dosage in Renal Failure1

“…Antibacterial drugs: 1 Pechere & Dugal (1979); 2 Noone (1984); 3 Rlstuccia & Cunha (1985); 4 Meyer (1981); 5 Hallynek et al (1981); 6 Craig at al. (1983); 7 Guay (1983); 8 Brogden et al (1976); 9 Tartaglione & Polk (1985); 10 Balant et al (1985); 11 Thompson & Wright (1983); 12 Clark et al (1983); 13 Derry (1981); 14 Leroy et al (1982); 15 Czerwinski & Federson (1979);16 Qulntillanl & Nightingale (1978); 17 Gambertoglio et al (1984); 18 Pontzer & Kaye (1984); 19 Lyon (1983); 20 Barriere & Mills (1982); 21 Doluiso (1982); 22 Konishi & Ozawa (1984); 23 Kampf et al (1981); 24 Ohkawa et al (1981); 25 Matzke & Keane (1983); 26 Richards …”