Page 1016 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

948 SECTION | XIV Poisonous Plants

VetBooks.ir TABLE 66.1 Physical and Chemical Properties of Taxine Alkaloids UV Maximum (nm) IR Maximum (cm )

21
Taxine
Molecular Formula
Melting Point ( C)

Taxine A C 35 H 47 NO 10 204 206 220, 255 1780, 1250
2-Deacetyltaxine A C 33 H 45 NO 9 224, 264 1734, 1691
Taxine B C 33 H 45 NO 8 115 210, 277 3578, 1730
Isotaxine B C 33 H 45 NO 8 282

O
HO OH
CH 3
H 3 C
H 3 C CH 3
O N
CH 3
H 3 C O
O
CH 3

O OH
H

R 1 O

Taxine alkaloids R 1
Taxine A Ac

2-Deacetyltaxine A H

FIGURE 66.1 Structural formulas for taxines A.

PHARMACOKINETICS/TOXICOKINETICS docetaxel is thought to be the result of metabolism by
CYP 3A4 to pharmacologically inactive oxidation pro-
For reasons likely related to their acute toxicity and lack
ducts that are excreted in the bile through a p-glycopro-
of pharmaceutical uses, pharmacokinetic studies on taxine
tein dependent mechanism (Gustafson et al., 2003;
alkaloids have not been well characterized. However,
Baker et al., 2006). Tissue distribution is extensive,
extensive pharmacokinetic studies have been reported for
except for the central nervous system (CNS) and testes.
the widely used antineoplastic drugs paclitaxel (isolated
The elimination half-life for paclitaxel is 5 7 h (two-
from T. brevifolia) and docetaxel (synthesized via a tax-
compartment model) or 20 h (three-compartment model),
ane precursor from T. baccata), which are also members
whereas the elimination half-life for docetaxel is 12 h
of the taxane diterpenoid family. These studies revealed
(two-compartment model) or 13 h (three-compartment
that both compounds are highly protein bound (.95%) in
model). Liver insufficiency or coadministration of com-
the serum and are metabolized by hepatic P450 enzymes.
pounds that modulate P450 activity may influence the
One differentiating characteristic noted was that paclitaxel
activity of these antineoplastic drugs and, presumably, the
exhibits nonlinear kinetics at therapeutic doses, whereas
activity of more acutely toxic members of the family,
the kinetics of docetaxel are linear. The linear kinetics of
such as taxines A and B (Brown, 2003).