Oral Absolute Bioavailability and Intravenous Dose‐Proportionality of Cefprozil in Humans

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Abstract
The absolute bioavailability (F) and dose proportionality of cefprozil were investigated in a parallel design study with an embedded two‐way crossover leg. Twenty‐four healthy male subjects divided into 3 dosing groups received a single 250‐, 500‐, or 1000‐mg dose of cefprozil by a 30‐minute intravenous infusion. Subjects assigned to the 500‐mg dose group also received a 500‐mg oral dose of cefprozil in crossover manner with a wash‐out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high‐pressure liquid chromatographic assay with UV detection methods. After the 250‐, 500‐, and 1000‐mg intravenous administration of cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 μg/mL, and area under the plasma concentration versus time proxies were 17.2, 31 A, and 58.1 μg · hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half‐life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration.