Comparative Human Oral Clinical Pharmacology of Cefadroxil, Cephalexin, and Cephradine

Abstract

At equivalent oral doses, cefadroxil has a longer serum half-life, slower urinary excretion rate, greater area under the serum level versus time curve than cephalexin or cephradine, and peak serum concentrations that are 75 to 80% those of cephalexin. The calculated, apparent in vivo volume of distribution of cefadroxil is greater than that of cephalexin. These properties infer greater persistence of cefadroxil in serum and urine and more prolonged in vivo bacterial exposure to cefadroxil than to cephalexin or cephradine. Neither cefadroxil nor cephalexin demonstrates drug accumulation on repeated administration. The serum levels achieved by cefadroxil are unaffected by food. The pharmacokinetic properties of cefadroxil are supportive of the development of clinical efficacy data which could indicate that cefadroxil could be administered at 12-h intervals.The studies reported here were undertaken to compare the pharmacokinetic properties in humans of the orally administered cephalosporin antibiotics cefadroxil, cephalexin, and cephradine (structures presented in Fig. 1) and to determine the factors which control their disposition in vivo. A companion paper presents data on the antibacterial activity of cefadroxil (1). The inhibitory activity of cefadroxil on clinical isolates was similar to that of cephalexin and cephradine. Cefadroxil was more effective than cephalexin against Streptococcus pyogenes and comparably as effective as cephalexin against Streptococcus pneumoniae, Staphylococcus aureus, and several gram-negative species in oral treatment of experimental infections in mice. MATERIALS AND METHODSBioassays for antibiotic activity in serum and urine were carried out by standard cup plate assay methodology (4) blood area nitrogen, serum glutamic pyruvic transaminase, bilirubin, urinalysis (including protein test, sugar and microscopy for casts and cells), and stool parasitological examination. Subjects with abnormal values or findings were not admitted into these studies. None of the subjects were to have taken any medication for 3 weeks prior to the study in which they participated.All subjects were fasted overnight before each study. Oral doses of drugs were always administered at 8:00 a.m. with 250 ml of water, and a further 250 ml of water was ingested every succeeding 2 h for the duration of the study. Except for portions of a study on the effect of food on drug bioavailability, the subjects maintained their fast for 2 h after drug administration.All studies were designed as balanced, randomized complete crossovers. There was a 6-day washout period between crossover legs.Study

Pharmacokinetics of Cephalexin after Intravenous and Single and Multiple Intramuscular Administration to Rabbit

“…The estimated valueswere similar to that in other species such as, rat (Tsai et al, 2000) dog (Carli et al, 1999) and cat (Albarellos et al, 2011). Accumulation index after multiple administrationswas closed to 1, reflecting cephalexin low accumulation capacity.Similar values are reported for humans after repeated oral administration (Pfeffer et al, 1977).…”

Comparison of Pharmacological and Antimicrobial Properties of Cefadroxil and Cephalexin

“…In parallel with these observations, cefadroxil concentrations in urine were also more sustained. Similar results were reported by Pfeffer et al (9). Except for minor differences, the MIC and MBC values of the two drugs against clinical isolates of S. pneumoniae, S. aureus, S. epidermidis, E. coli, and Klebsiella species were similar.…”

Comparative Pharmacokinetics of Cephalexin, Cefaclor, Cefadroxil, and CGP 9000

“…In experimental infections in animals, CGP 9000 proved to be superior to cephalexin (27). The bioavailability of cephadroxil administered orally is superior to that of cephalexin (10,22). In the present study, the pharnacokinetic parameters of these three new substances and cephalexin were compared after oral administration to each of 12 fasting subjects.…”