Sixteen healthy male volunteers participated in a randomized, balanced, three-way crossover study comparing the pharmacokinetics of cefmetazole, cefoxitin, and cefmetazole with probenecid pretreatment. Single 2-g doses of cefmetazole sodium and cefoxitin sodium were given intravenously as a 5-min infusion. Concentrations of cefmetazole and cefoxitin were determined by using a specific semiautomated highperformance liquid chromatographic method. Concentration-time profiles of cefmetazole and cefoxitin declined in a biexponential manner from peak levels. Compared with cefoxitin, cefmetazole had a significantly (P < 0.05) higher mean (± standard error of the mean) peak concentration in serum (290 ± 11 versus 244 ± 10 ,ig/ml), a longer terminal disposition half-life (1.50 ± 0.14 versus 0.81 ± 0.04 h), lower systemic clearance (111.7 ± 4.7 versus 279 ± 12 ml/min) and renal clearance (78.7 ± 4.3 versus 221 ± 14 ml/min) of intact drug, and a slightly smaller steady-state volume of distribution (10.3 ± 0.21 versus 12.8 ± 0.48 liters). Mean recoveries of cefmetazole and cefoxitin in urine were approximately 71 and 77%, respectively. Pretreatment of volunteers with probenecid (1 g orally) significantly (P < 0.05) increased concentrations of cefmetazole in serum 1 h after drug administration without significantly increasing maximum concentrations in serum. Mean areas under the concentration-time curve (466 ± 27 versus 295 + 13 ,ug h/ml) and terminal disposition half-lives (2.27 ± 0.13 versus 1.50 ± 0.14 h) of cefmetazole increased. Systemic clearance (72.1 ± 4.0 versus 111.7 ± 4.7 ml/min) and renal clearance (47.4 ± 4.0 versus 78.7 ± 4.3 ml/min) of intact antibiotic decreased. Mean recoveries (65.9 ± 3.7 versus 71.0 ± 3.2%) of intact cefmetazole in urine were not significantly (P > 0.05) different. Elimination of cefmetazole in urine was also significantly prolonged by probenecid, with substantial concentrations of cefmetazole ('20 ,g/ml) found in the 12-to 24-h urine collection for 14 of 16 volunteers. The results show that cefmetazole remains at clinically relevant concentrations (1 to 2 ,ug/ml) approximately twice as long as cefoxitin, that serum cefmetazole can be maintained longer at clinically significant concentrations with preadministration of probenecid, and that cefmetazole is partially eliminated by renal tubule secretion.Cefmetazole sodium is a semisynthetic derivative of cephamycin C (5) having a very broad antibacterial spectrum in vivo and in vitro, including the majority of clinically important gram-positive and gram-negative aerobic and anaerobic bacteria (4). The MICs of cefmetazole for a number of gram-positive and gram-negative organisms are in the range of 0.5 to 4.0 ,wg/ml (4,12). Clinical studies have confirmed its effectiveness, when administered parenterally, in the treatment of a number of infections (12) and as a prophylaxis for prevention of postsurgical wound infection (9).Pharmacokinetic studies in healthy human volunteers administered intravenous doses of cefmetazole sodium have been conducte...

No abstract

No abstract

No abstract

Triesters (III) of phosphoric-carbonic anhydride were prepared by reaction of silver dibenzyl phosphate with an alkyl chloroformate. The anhydrides were readily hydrolyzed to dialkyl phosphate, carbon dioxide, and the corresponding alcohol. Hydrolysis in 1H0-enriched water indicated carbon-oxygen fission. The hydrolysis is subject to general base catalysis and to catalysis by certain metal ions.