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Absolute Bioavailability and Noncompartmental Analysis of Intravenous and Intramuscular Cefotan® (Cefotetan) in Normal Volunteers
Author(s) -
Zimmerman James,
Cohen Albert,
Thyrum Per
Publication year - 1989
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1989.tb03304.x
Subject(s) - cefotetan , pharmacokinetics , volume of distribution , bioavailability , medicine , urine , intramuscular injection , volunteer , anesthesia , chemistry , pharmacology , antibiotics , biochemistry , antibiotic resistance , imipenem , agronomy , biology
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 μg/mL, 4.54 ± 1.05 hours, and 29.1 ± 3.8 mL/min/1.73 m 2 , 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 μg/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 percentages 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. The near coincidence of plasma mean cefotetan concentrations starting at 2 hours after intramuscular and intravenous administration suggests that intramuscular cefotetan is a reasonable alternative to intravenous dosing in the treatment of infections due to susceptible bacteria.