Cefotetan clinical pharmacology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]
High plasma levels of cefotetan are attained after intravenous and intramuscular administration of single doses to normal volunteers.
The plasma elimination half-life of cefotetan is 3 to 4.6 hours after either intravenous or intramuscular administration.
Repeated administration of CEFOTAN does not result in
accumulation of the drug in normal subjects.
Cefotetan is 88% plasma protein bound.
No active metabolites of cefotetan have been detected; however, small amounts (less than 7%) of cefotetan in plasma and urine may be converted to its tautomer, which has antimicrobial activity similar to the parent drug.
In normal patients, from 51% to 81% of an administered dose of CEFOTAN is excreted unchanged by the kidneys over a 24 hour period, which results in high and prolonged urinary concentrations. Following intravenous doses of 1 gram and 2 grams, urinary concentrations are highest during the first hour and reach concentrations of approximately 1700 and 3500 µg/mL respectively.
In volunteers with reduced renal function, the plasma half-life of cefotetan is prolonged. The mean terminal half-life increases with declining renal function, from approximately 4 hours in volunteers with normal renal function to about 10 hours in those with moderate renal impairment. There is a linear correlation between the systemic clearance of cefotetan and creatinine clearance. When renal function is impaired, a reduced dosing schedule based on creatinine clearance must be used. (see DOSAGE AND ADMINISTRATION).
In pharmacokinetics studies of eight elderly patients (greater than 65 years) with normal renal function and six healthy volunteers (aged 25 to 28 years), mean (± 1sd) Total Body Clearance (1.8(0.1) L/h vs. 1.8 (0.3) L/h) and mean Volume of Distribution (10.4(1.2) L vs. 10.3 (1.6)L) were similar following administration of a one gram intravenous bolus dose.
Therapeutic levels of cefotetan are achieved in many body tissues and fluids including:
References
http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/50588slr027_cefotan_lbl.pdf