Premium
Effect of dose and food on the bioavailability of cefuroxime axetil
Author(s) -
Finn A.,
Straughn A.,
Meyer M.,
Chubb J.
Publication year - 1987
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510080604
Subject(s) - cefuroxime , bioavailability , crossover study , pharmacokinetics , urine , medicine , oral administration , dosing , pharmacology , absorption (acoustics) , dosage form , area under the curve , chemistry , antibiotics , biochemistry , physics , alternative medicine , pathology , acoustics , placebo
Abstract Cefuroxime axetil is an ester pro‐drug which permits the oral administration of cefuroxime. This study was designed to evaluate the dose proportionality of four different doses administered after a meal and to determine the absolute bioavailability of cefuroxime axetil administered with and without food. The study was a six‐way randomized crossover trial in 12 normal male volunteers. Subjects received an intravenous dose of cefuroxime (500 mg) and five oral doses of cefuroxime axetil (125, 250, 500‐twice, 1000 mg). The intravenous dose and one of the 500 mg doses was administered after an overnight fast. The other four oral doses were administered after a standard meal. Blood samples were collected prior to each dose and serially for 12 h after the dose. Urine was collected for 24 h. Plasma and urine samples were analysed for cefuroxime by high pressure liquid chromatography. There was a linear relationship between the fed dose and both the area under the plasma concentration time curve ( r 2 = 0.958) and the peak plasma concentration ( r 2 = 0.943). Based on a comparison of the AUC for the oral and intravenous data, 36 per cent of the fasting and 52 per cent of the fed 500 mg doses were absorbed. The mean peak plasma concentration was 43 per cent greater after the fed dose than the fasting dose. A plot of the mean fraction of unabsorbed drug versus time reveals that absorption is an apparent zero order process from 0.5 to 3 h after dosing.