Concentrations of cefmetazole in plasma and tissue resulting from peri-incisional administration before appendectomy

Abstract

The levels of cefmetazole in plasma and tissue were determined after injection of a dose of 30 mg/kg into the zone of the wound of each of 15 patients undergoing appendectomy. The mean plasma levels of cefmetazole at the start and end of surgery (8.9 ± 2.4 and 31.7 ± 6.4 min after dosage) were 21.1 and 59.0 ,ug/ml, respectively; concentrations of the drug were 14.6 and 4,486.9 ,ug/g in skin, 9,165.0 and 1,756.4 ,ug/g in subcutaneous tissue, and 8,669.6 and 2,022.9 lug/g in muscle.Infection of surgical wounds, above all in gastrointestinal tract operations, is undoubtedly endogenous in origin (2). According to Davidson et al., the most important pathogenetic factor is the presence of bacteria in the incision itself at the moment of suturing the wound (1). Even though intravenous administration of antibiotics has proved efficient, significantly reducing the incidence of infection in surgical wounds, prophylactic measures, including topical application of antibiotics (2) to achieve high local drug concentrations, have also been useful. The aim of the present study was to determine whether peri-incisional administration of cefmetazole would produce sufficiently high levels of the drug in tissue to guarantee clinical efficiency.The tissue penetration of cefmetazole was studied in 15 adult patients with acute appendicitis (5 males, 10 females) with an age range of 14 to 37 years and a weight range between 47 and 71 kg. The concentrations of urea, creatinine, glucose, proteins, and albumin were measured in all patients; no additional diseases to that responsible for the operation were found. Patients with a history of allergy to the penicillins or cephalosporins, as well as those who had received any medication during the 7 days before the operation, were excluded from the study. Informed consent was obtained previously in all cases.Cefmetazole was administered at a dose of 30 mg/kg (1 g/10 ml). After anesthesia, the skin and subcutaneous tissue at the projected incision site (3 to 5 cm) were infiltrated with the antibiotic. The incision was performed, the time elapsed was noted, and samples of skin, subcutaneous tissue, and blood were taken immediately. Infiltration of the muscle layer was carried out after opening the fascia. The same sampling procedure was repeated, after removal of the appendix, and the time elapsed after infiltration was noted. column (Waters Associates) with a mobile phase of 10 to 15% acetonitrile in 0.005 M citrate buffer (pH 5.4). The flow rate was maintained at 1.0 ml/min, and all operations were carried out at room temperature. Calibration of cefmetazole levels was performed based on the peak height ratio of cefmetazole to the internal standard.All the results obtained from the concentrations in plasma and tissue at the start and end of the operation, as well as the relationships of the respective values at the start and end, were subjected to Student's t test (4) to check the possible existence of statistically significant differences. Table 1 shows the concentrations of cefmetazole in plas...

Association of serum and fat tissue antibiotic concentrations with surgical site infections in lower gastrointestinal surgery

“…6 After intravenous administration of CMZ in patients undergoing appendectomy, the antibiotic levels tended to decrease during surgery. 30 Isla et al recommended the administration of CFX every 1.5 hours for patients with a Ccr of 60 to 80 mL/min and once every 1 hour for those whose Ccr exceeded 100 mL/min during colorectal surgery. 31 The half-life of CMZ is 1.3 hours; therefore, CMZ is administered every 3 hours and readministered at intervals of twice the half-life, 32 which was the method that was followed in the cases included in this study.…”

Pharmacokinetic parameters from data relating to the plasma and biliary excretion kinetics of cefmetazole in rats

“…This cephalosporin has proved to be efficacious against Gram-positive and Gram-negative microorganisms (3,4) and its phannacokinetic characteristics have been well studied in human subjects at the level of its plasma kinetics (5)(6)(7)(8)(9), although less is known about the kinetics of its biliary excretion.…”