Allometric analysis of thiamphenicol disposition among seven mammalian species

Abstract

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.

Pharmacokinetics of thiamphenicol in Japanese quails (Coturnix japonica) after single intravenous and oral administrations

“…and Gram -ve bacteria in poultry (Switala & Debowy, 2005;Switała et al, 2007;Wei et al, 2016). Due to its broad antibacterial spectrum, TP has the potential to become a valuable antibiotic in the treatment and control of a wide range of alimentary and respiratory tracts infections of bacterial origin in poultry (Castells et al, 2001;Castells et al, 2000).…”

Concepts and Issues with Interspecies Scaling in Zoological Pharmacology

“…31, 60,71,90,93,94 The differences are not just in phase I metabolism but also in phase II. 15,17,91 Other factors, such as cytochrome P450 isozyme expression, hepatic extraction ratio, species-specific hepatic blood flow, and other speciesspecific hepatic physiology and anatomy also have a role in drug metabolism. All of these potential differences in drug metabolism make extrapolation of pharmacokinetic parameters for metabolized drugs difficult, if not impossible.…”

Capillary electrophoretic determination of thiamphenicol in turkeys serum and its pharmacokinetic application

“…and control of a wide range of respiratory and alimentary tract infections of bacterial origin in livestock of mammals, poultry and recently it has been adopted for the treatment of several infectious diseases in fish [4,5].…”