Allometric analysis of thiamphenicol disposition among seven mammalian species

The pharmacokinetics of thiamphenicol (TAP), a broad-spectrum antibiotic, w as determined in male mice, rats, rabbits, dogs, pigs, sheep and calves, Th e relationship between the main pharmacokinetic parameters of TAP and body weight (W) was studied across these seven mammalian species, using double-l ogarithmic plots. The experimental values of volume of distribution (V-ss), clearance (Cl) and elimination half-life (t(1/2)beta) were plotted, and ex trapolated values were determined from corresponding allometric equations. These parameters were fitted to the following equations: V-ss=0.98W(0.92) C l=15.80W(0.76) and t(1/2)beta0.94W(0.20), and present good correlation (V-s s: r(2) = 0.997, P < 0.001; CI: r(2) = 0.976, P < 0.001, t(1/2)beta: r(2) = 0.852, P < 0.005), that is expected of a drug eliminated primarily by rena l glomerular filtration, with insignificant hepatic metabolism. For the t(1 /2)<beta> the extrapolated and observed values were similar. The extrapolat ed values of CI were close to the experimental values, except for the mouse and pig mean percent error [(M.E.) equal to 62 and 119%, respectively], wh ile the extrapolated and observed values for the V-ss were very similar. Th e comparison between experimental and extrapolated values suggests that it could be possible to extrapolate, with good prediction, the kinetic paramet ers of this drug for mammalian species, using allometric scaling, except fo r the species that eliminate the drug by a combination of renal excretion a nd hepatic metabolism.