Pharmacokinetics and tissue penetration of single-dose cefotetan used for antimicrobial prophylaxis in patients undergoing colorectal surgery

Martin, Claude; Portet, C.; Lambert, Dominique; Bruguerolle, Bernard; Sastre, B.; Micco, P. De

doi:10.1128/aac.36.5.1115

Cited by 16 publications

(13 citation statements)

References 13 publications

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“…Among patients undergoing colorectal surgery, cefotetan serum concentrations were 163, 73 and 64 mg/L, 33, 151 and 216 minutes, respectively, after a single 2.0g IV bolus dose (Martin et al 1992). Similarly, cefotetan and cefoxitin serum concentrations 80 minutes after administration of single 2.0g IV doses were 108 and 34 mg/L, respectively (Quintiliani et al 1985).…”

Section: Absorptionmentioning

confidence: 94%

Clinical Pharmacokinetics of Cefotetan

Martin

Thomachot

Albanèse

1994

Clinical Pharmacokinetics

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Cefotetan is a 7-alpha-methoxy beta-lactam. A long serum half-life and resistance to beta-lactamase hydrolysis have made cefotetan an attractive chemotherapeutic agent, and the results of clinical trials worldwide have demonstrated its efficacy in a wide variety of clinical situations. Cefotetan can be administered intravenously (bolus or infusion) or intramuscularly with lidocaine (lignocaine) 0.5%. Mean peak plasma concentrations are almost linearly related to dose. The volume of distribution is between 8 and 13L and is not different from other cephalosporins. No accumulation is seen after repeated doses and no metabolite has been detected in either plasma or urine. Total body clearance is 1.8 to 2.9 L/h. Renal clearance accounts for about 64 to 84% of a dose, and 75% of a dose is excreted in the urine within 24 hours. The plasma elimination half-life is between 3 and 4 hours after intravenous and intramuscular doses. Half-life is considerably prolonged in patients with renal impairment (up to 10 hours). Cefotetan concentrations are likely to be active against susceptible bacteria in most tissues and body fluids. Breast milk and cerebrospinal fluid concentrations are low. The recommended dosage is 1g every 12 hours, increasing to 2g in severe infections and 3g in life-threatening infections. In surgical prophylaxis, a single dose of 2g is given with the induction of anaesthesia; an additional dose of 2g may be administered 12 hours later. In children over 6 months, the recommended dosage is 30 mg/kg given 12-hourly. In patients with a creatinine clearance of 10 to 40 ml/min (0.6 to 2.4 L/h), the dose is halved or the dosage interval is doubled. When creatinine clearance is less than 10 ml/min (0.6 L/h), the dose is quartered or the dosage interval quadrupled.

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Section: Absorptionmentioning

confidence: 94%

Clinical Pharmacokinetics of Cefotetan

Martin

Thomachot

Albanèse

1994

Clinical Pharmacokinetics

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“…In the present study, the extend of penetration of both compounds was maintained throughout the surgical procedure probably because of the second injection performed after 120 min. This emphasizes the need for repeated injections of drugs with shorter half-lives (4,8,13,18,19). Had this second injection not been performed, decreased concentrations of both compounds would probably have been measured in fatty tissues, with an increased risk of postoperative infection.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have established the basic principles of antibiotic prophylaxis in surgical procedures, and the main points are that (i) the antibiotic must reach the tissues involved before surgery allows bacterial contamination, and (ii) the drug must attain and maintain concentrations in serum and tissues high enough to inhibit the growth of contaminating pathogens (4,6,8,13,18).…”

Section: Discussionmentioning

confidence: 99%

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Comparison of concentrations of two doses of clavulanic acid (200 and 400 milligrams) administered with amoxicillin (2,000 milligrams) in tissues of patients undergoing colorectal surgery

Martin

Mallet

Sastre

et al. 1995

Antimicrob Agents Chemother

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The concentrations of clavulanic acid and amoxicillin were determined in sera and different abdominal tissues of 17 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 were given 200 mg of clavulanic acid with 2,000 mg of amoxicillin and patients in group 2 received 400 mg of clavulanic acid with 2,000 mg of amoxicillin. In both groups, the initial dose was administered again after 2 h. Blood samples were collected to determine peak and trough antibiotic levels. Serial blood samples were also collected at predetermined periods (opening and closure of the abdominal cavity and surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Increasing the dose of clavulanic acid to 400 mg resulted in significantly higher peak and trough levels in serum (P < 0.03). Following the injection of 400 mg, mean concentrations of clavulanic acid in the fatty tissues were significantly increased at the time of opening (P < 0.02). The concentrations of clavulanic acid and amoxicillin in fatty tissues were 17 to 52% and 12 to 23% of the levels in sera, respectively. In the colonic wall, the concentrations of clavulanic acid and amoxicillin were 52 to 63% and 49 and 27% of the levels in sera, respectively. In sera, clavulanic acid given at a dose of 200 or 400 mg reached or exceeded the concentrations found to be effective in vitro to reduce the MICs of amoxicillin from the resistant to the susceptible category for 90% of the potential pathogens. In most of the tissues investigated, increasing the dose of clavulanic acid to 400 mg resulted in a significantly higher number of samples with concentrations found to be effective in vitro (72 versus 11%; P < 0.05). In conclusion, increasing the dose of clavulanic acid to 400 mg resulted in higher levels in sera and improved penetration into the abdominal tissues in patients undergoing colorectal surgery.

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“…Currently, several studies on the clinical pharmacokinetics following intravenous dose in healthy volunteers (Nakagawa et al 1982;Yates et al 1983;Adam et al 1983;Guibert et al 1983;Zimmerman et al 1989;Welage et al 1989Welage et al , 1990Shi et al 2010), patients undergoing biliary surgery (Cristiano et al 1988;Cherrier et al 1993), patients undergoing colorectal surgery (Quintiliani et al 1988;Martin et al 1992), or patients with impaired renal function (Ohkawa et al 1983;Smith et al 1986), in which the primary focus was the total-CTT (R ? S epimers) have been published.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic differences between the epimers of cefotetan disodium after single intravenous injection in healthy Chinese volunteers

Liu

et al. 2011

Eur J Drug Metab Pharmacokinet

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The pharmacokinetic behaviors of the epimers of cefotetan disodium (R-CTT, S-CTT) after a single intravenous injection dose in healthy Chinese volunteers were explored in this study. In an open-label, randomized, three-way, cross-over study, 12 volunteers (6 females and 6 males) received a cross-over fashion doses of 0.5, 1.0, and 2.0 g of cefotetan disodium, separated by washout periods of 7 days. The plasma concentrations of both epimers were measured by validated high-performance liquid chromatography assays. Pharmacokinetic parameters of R-CTT, S-CTT, and total-CTT (R + S mixture) were calculated using a noncompartmental analysis. Generally, the R and S epimers showed different pharmacokinetic behaviors. Following 0.5, 1.0, and 2.0 g doses of cefotetan disodium, values of the total area under the plasma concentration-time curve (AUC(0-∞)) were 124.23 ± 19.54, 231.34 ± 39.34, and 459.09 ± 80.65 for R-CTT; 100.95 ± 14.19, 193.80 ± 30.42, and 372.66 ± 67.32 for S-CTT, respectively. Total body clearance values were 4.13, 4.43, and 4.46 L/h for R-CTT and 5.05, 5.28, and 5.50 L/h for S-CTT, respectively. Mean plasma elimination half-life (t (1/2)) values of R-CTT were 4.16, 4.13, and 4.01 h for 0.5, 1.0, and 2.0 g doses, respectively, and those of S-CTT were 3.15, 3.25, and 3.21 h. There were significant differences in t (1/2) between the two epimers (P < 0.05). The t (1/2) of R-CTT was 28% longer than that of S-CTT, which indicated that the elimination of the S-CTT was greater than that of the R-CTT. All treatments were well tolerated.

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Pharmacokinetics and tissue penetration of single-dose cefotetan used for antimicrobial prophylaxis in patients undergoing colorectal surgery

Cited by 16 publications

References 13 publications

Clinical Pharmacokinetics of Cefotetan

Clinical Pharmacokinetics of Cefotetan

Comparison of concentrations of two doses of clavulanic acid (200 and 400 milligrams) administered with amoxicillin (2,000 milligrams) in tissues of patients undergoing colorectal surgery

Pharmacokinetic differences between the epimers of cefotetan disodium after single intravenous injection in healthy Chinese volunteers

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