Allometric analysis of thiamphenicol disposition among seven mammalian species.
The pharmacokinetics of thiamphenicol (TAP), a broad-spectrum antibiotic, was determined in male mice, rats, rabbits, dogs, pigs, sheep and calves. The relationship between the main pharmacokinetic parameters of TAP and body weight (W) was studied across these seven mammalian species, using double-logarithmic plots. The experimental values of volume of distribution (Vss), clearance (Cl) and elimination half-life (t(1/2)beta) were plotted, and extrapolated values were determined from corresponding allometric equations. These parameters were fitted to the following equations: Vss=0.98W0.92, Cl=15.80W0.76 and t(1/2)beta=0.94W0.20, and present good correlation (Vss: r2=0.997, P < 0.001; Cl: r2=0.976, P < 0.001, t(1/2)beta: r2=0.852, P < 0.005), that is expected of a drug eliminated primarily by renal glomerular filtration, with insignificant hepatic metabolism. For the t(1/2)beta, the extrapolated and observed values were similar. The extrapolated values of Cl were close to the experimental values, except for the mouse and pig mean percent error [(M.E.) equal to 62 and 119%, respectively], while the extrapolated and observed values for the Vss were very similar. The comparison between experimental and extrapolated values suggests that it could be possible to extrapolate, with good prediction, the kinetic parameters of this drug for mammalian species, using allometric scaling, except for the species that eliminate the drug by a combination of renal excretion and hepatic metabolism.
Castells
G
G
Department of Pharmacology and Therapeutics, School of Veterinary Science, Universitat Autònoma de Barcelona, Bellaterra, Spain. gcastells@quiro.uab.es
Capece
B P
BP
Pérez
F
F
Martí
G
G
Arboix
M
M
Cristòfol
C
C
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight; D002417:Cattle; D004285:Dogs; D007275:Injections, Intravenous / Q000662:veterinary; D016015:Logistic Models; D008297:Male; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D011817:Rabbits; D051381:Rats; D012756:Sheep; D013552:Swine; D013839:Thiamphenicol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D013839:Thiamphenicol