Absolute Bioavailability and Noncompartmental Analysis of Intravenous and Intramuscular Cefotan® (Cefotetan) in Normal Volunteers

Abstract

Cefotetan (1 g) was administered to 12 normal volunteers as a 30 minute intravenous infusion and as an intramuscular injection. The pharmacokinetic parameters were estimated using noncompartmental analysis. The mean +/- SD maximum plasma concentration, terminal half-life, and systemic clearance after intravenous infusion were 158 +/- 21 micrograms/mL, 4.54 +/- 1.05 hours, and 29.1 +/- 3.8 mL/min/1.73 m2, respectively. Renal clearance and nonrenal clearance accounted for 63.1% and 36.9% of the systemic clearance, respectively. The mean +/- SD maximum plasma concentration, time to maximum concentration, terminal half-life, and absolute bioavailability after intramuscular injection were 75.5 +/- 8.7 micrograms/mL, 1.33 +/- 0.48 hours, 4.32 +/- 0.77 hours, and 0.931 +/- 0.193, respectively. Moment analysis gave average +/- SD mean residence times (MRT) of 4.98 +/- 0.75 and 5.86 +/- 0.77 hours after intravenous and intramuscular administration, respectively. The average +/- SD mean absorption time (MAT) after intramuscular injection was 1.11 +/- 0.57 hours. The mean +/- SD steady-state volume of distribution after intravenous infusion was 0.129 +/- 0.024 L/kg. The mean +/- SD cumulative percentage of the dose excreted in the urine in 24 hours were 61.1 +/- 11.4% and 50.4 +/- 13.5% after intravenous and intramuscular dosing, respectively. The maximum urinary cefotetan concentrations occurred during the first 2 hours after dosing by both routes of administration. Cefotetan tautomer was detected in the plasma and urine of all subjects after both routes of administration, but the mean concentrations were only minimal compared to those for cefotetan. In conclusion, intramuscular cefotetan (1 g) is rapidly and almost completely absorbed.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…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.…”