Saturable rate of cefatrizine absorption after oral administration to humans.
This study examined the absorption kinetics of cefatrizine, an amino-beta-lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first-order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration-time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier-mediated transport previously reported to occur in the gastrointestinal tract of rats.
Reigner
B G
BG
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
Couet
W
W
Guedes
J P
JP
Fourtillan
J B
JB
Tozer
T N
TN
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D002436:Cefatrizine / Q000008:administration & dosage / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D013997:Time Factors
D002511:Cephalosporins; D002436:Cefatrizine