due to the long gastrointestinal transit times of greater than one week in boid snakes
(Secor et al. 1994 ), which allow for a xenobiotic to undergo repeated enterohepatic
recirculation during the course of a single drug administration.
As azithromycin metabolism, in mammals, is mediated by several cytochrome
P450 isoforms, it is possible that these systemic metabolites are formed through the
action of novel cytochrome P450 isoforms, the unique gastrointestinal physiology
of the ball python, or a combination of both. This may be compared with the effect
that is produced by sustained-release oral formulations in mammals. This phenom-
enon would be expected to correspondingly prolong tissue concentrations of the
parent compound and its metabolites (Hunter et al. 2003 ; Fig. 2 ). These factors are
also likely to have an impact on variable bioavailability depending on time of
feeding in snakes. Therefore, rate and extent of oral drug absorption may be
dependent on time after feeding. In addition to differences in gastrointestinal
physiology, differences in preferred optimal temperature zone could also have a
role in interspecies extrapolation, but the effects of environmental temperature on
pharmacokinetics are less well understood than the feeding effect on gastrointesti-
nal physiology and drug absorption (Coke 2000 ).
In veterinary medicine, various methods have been used in attempts to extrapo-
late between species and feeding states to predict safe and effective dosage regi-
mens. The simplest and typical method of extrapolating a dosage from a domestic
Fig. 2Metabolite structures and possible metabolic pathways of azithromycin in the ball python
(Hunter et al. 2003 )
142 R.P. Hunter