Forecasting cephalosporin and monobactam antibiotic half-lives in humans from data collected in laboratory animals.
The postdistribution half-lives of 10 cephalosporin and 2 monobactam antibiotics in humans were predicted from data obtained in other mammals. This forecasting was accomplished with the allometric equation t1/2 = aWb, where a is the y intercept and b is the slope obtained from the log-log plot of antibiotic half-life (t1/2) versus body weight (W). Dimensionless similarity criteria were used to produce a biological clock for ceftizoxime elimination. The creation of the biological clock, which measured physiologic time (heartbeats) rather than chronologic time (minutes), demonstrated that ceftizoxime half-life was identical in five mammals. This methodology will contribute to infectious disease research through a greater understanding of pharmacokinetic scaling in mammals.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002511:Cephalosporins / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D006207:Half-Life; D000882:Haplorhini; D006801:Humans; D007700:Kinetics; D051379:Mice; D011817:Rabbits; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D013045:Species Specificity
D000900:Anti-Bacterial Agents; D002511:Cephalosporins