| This study was undertaken to clarify the inconsistencies reported in the literature regarding the effect of food on the bioavailability of oral cephalosporins and to gain insight concerning their absorption kinetics and relevants compartment models.; The relative bioavailability of cephalexin, cephradine, and cefaclor was examined after single 500 mg oral doses to 8 healthy male volunteers after an overnight fast and immediately following a standard breakfast. Plasma and urinary concentrations were determined by HPLC procedures.; Under fasting conditions, all three cephalosporins were absorbed rapidly, giving rise to mean peak plasma concentrations of 16.8, 19.4, and 10.3 mcg/ml for cephalexin, cephradine, and cefaclor, respectively, at approximately 1 hr. After postprandial doses, C(,max) values were reduced, t(,max) values were increased, and areas under plasma concentration-time curves were unaffected for all three cephalosporins. Under fasting conditions, the total 12 hr urinary recovery of cephalexin, cephradine, and cefaclor was 88.5, 89.1, and 73.7% of the administered dose. Urinary excretion was delayed, but total urinary recovery was not significantly affected by food. Lower plasma concentrations and reduced urinary recovery of cefaclor are probably due to its chemical instability.; The plasma concentrations of all three cephalosporins were better described by a one-compartment model with zero-order absorption under fasting conditions. However, under nonfasting conditions, plasma concentrations could be adequately described by either the zero-order or first-order absorption model with 'flip-flop' characteristics.; Relative bioavailability was examined by model-independent and model-dependent parameters generated from plasma profiles, cumulative relative fraction absorbed plots, urinary excretion data, the Kwan-Till method, and statistical moment analysis. The results confirm that food causes a delay in absorption of the cephalosporins without significantly affecting their overall absorption efficiency.; The observed changes in plasma cephalosporin concentrations after single doses are likely to occur after repeated doses. The clinical significance of the reduced drug concentration after post-prandial doses must be evaluated in light of the microbiological activity of the cephalosporins and the sensitivity of the target organisms. |
