Pharmacokinetics and dose proportionality of cefmetazole in healthy young and elderly volunteers.

The pharmacokinetics and dose proportionality of cefmetazole were studied in 24 healthy volunteers (12 young and 12 elderly). Each volunteer received single 0.5-, 1-, and 2-g doses of cefmetazole administered intravenously over 5 min according to a three-way crossover design. Serial plasma and urine samples were collected over a 24-h period following dosing and assayed for cefmetazole by a high-performance liquid chromatography method. Results of the dose proportionality portion of the study indicated that cefmetazole pharmacokinetics are linear and proportional with dose in both age groups. Comparisons of pharmacokinetic parameters between the young and elderly groups indicated that the systemic clearance was significantly lower in elderly than in young volunteers (92.4 versus 112 ml/min). Additionally, creatinine clearance was significantly lower in elderly (74.1 ml/min) than in young (92.9 ml/min) subjects. No significant differences between age groups were observed for volume of distribution, urinary recovery, terminal half-life, nonrenal clearance, or renal clearance, although half-life was slightly prolonged in elderly volunteers relative to that in young volunteers (1.54 versus 1.34 h), and renal clearance was slightly lower in elderly than in young volunteers (83.7 versus 96.1 ml/min). Both systemic and renal clearance were significantly correlated with creatinine clearance. These results indicate that the observed age-related differences in the pharmacokinetics of cefmetazole are most likely due to differences in renal function between the two age groups. The small reduction in cefmetazole elimination in the elderly would not warrant dose adjustment in this population.

Disposition of cefmetazole in healthy volunteers and patients with impaired renal function.

The disposition of cefmetazole was studied in 25 subjects with various degrees of renal function after a 1,000-mg, constant-rate, 30-min intravenous infusion of cefmetazole sodium. In six subjects with creatinine clearance (CLCR) of greater than 90 ml/min per 1.73 m2 (group 1), the terminal elimination half-life (t1/2 beta) was 1.31 +/- 0.54 h (mean +/- standard deviation), cefmetazole total body clearance (CLP) was 132.8 +/- 25.1 ml/min per 1.73 m2, and volume of distribution at steady state was 0.165 +/- 0.025 liter/kg. The fraction of dose excreted unchanged in the urine was 84.0% +/- 26.1%. Subjects with CLCRS of 40 to 69 (group 2, n = 6) and 10 to 39 (group 3, n = 6) ml/min per 1.73 m2 demonstrated prolongation of the t1/2 beta (3.62 +/- 1.06 and 5.93 +/- 1.81 h, respectively) and significant reductions in cefmetazole CLP (52.8 +/- 14.3 and 30.2 +/- 10.2 ml/min per 1.73 m2, respectively), compared with group 1. In seven subjects on chronic hemodialysis (group 4) studied during an interdialytic period, the cefmetazole t1/2 beta was increased to 24.10 +/- 8.12 h and the CLP was reduced to 6.8 +/- 2.1 ml/min per 1.73 m2. Cefmetazole CLP correlated positively with CLCR (r = 0.951, P less than 0.001): CLP = (1.181 . CLCR) -- 0.287. The disposition of cefmetazole was also assessed in six group 4 subjects during an intradialytic period. The t1/2 beta during hemodialysis (2.09 +/- 0.69 h) was significantly shorter than that observed during the interdialytic period. The hemodialysis clearance of cefmetazole was 86.1 +/- 20.1 ml/min, and the fraction of cefmetazole removed during hemodialysis was 59.8% +/- 5.9%. It is recommended that patients with renal insufficiency received standard doses of cefmetazole at extended intervals and patients on maintenance hemodialysis received standard doses after hemodialysis.

[Urinary tract infection associated with urinary calculi. 2. Effects of antibiotics on bacteria within infected stones].

We investigated the effect of antimicrobial agents against bacteria within infected stones. Cefmetazole (CMZ) was found to have equally strong activities against gram-positive and gram-negative bacteria isolated from the stones. In addition, CMZ was excreted in the urine from the affected kidney in high concentrations and was penetrated into the stone to some extent in vitro. However, preoperative administration of CMZ did not so significantly eradicate bacteria within the stones. Stones may function as a sanctuary for organisms and may attenuate the effects of antibiotics against them. Therefore, to treat urinary tract infection associated with urinary calculi, complete extirpation is necessary. In recent years, ultrasonic and other types of stone crushing methods are in wide use. CMZ or other effective antibiotics may become useful for the perioperative management of infected urinary stones.