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were not calculated. The chromatographic curves from both treatments showed
some time-dependent unknown peaks, likely metabolites not currently identified.
17.4 Discussion
The administration of tramadol has been widely studied in the recent past in both
equine (Giorgi et al.
2007
) and ruminant species (de Sousa et al.
2008
; Elghazali
et al.
2008
). M1 concentrations are low in plasma from these species with an
assumed lack of effectiveness for pain therapies. This study reports for the first
time the plasma concentration of the main metabolites of tramadol (M1, M2, and
M5) in the camelid species alpaca (
V. pacos
). To estimate the onset time and the
duration of action following IM and IV injection, the clinically relevant therapeutic
parameters
t
e
and
t
e
were calculated for an assumed MEC (Malonne et al.
2004
).
A target plasma concentration of tramadol of 100 ng/mL was clinically effective in
the treatment of mild to moderate pain in humans (Malonne et al.
2004
). The
D
t
e
values for IM and IV administration were similar, with small differences likely due
to different initial time courses of absorption.
These data assume that the MEC as calculated for humans is relevant for alpacas
and should be integrated with further pharmacodynamic studies. To determine the
analgesic effect of tramadol in humans, some authors have used the plasma
concentration of M1, the molecule indicated as responsible for most of the thera-
peutic effects (Garrido et al.
2003
). In the present study, the metabolite M1 was
detected at a concentration at or lower than the MEC (0.040
D
0.030
m
g/mL)
reported for humans (Grond and Sablotzki
2004
), and calculation of
t
e
for M1
was not possible. The low concentrations of the active metabolite are in accordance
with earlier studies in goats (de Sousa et al.
2008
), equines (Giorgi et al.
2007
), and
dogs (KuKanich and Papich
2004
; Giorgi et al.
2009a
,
b
,
c
), and in contrast to those
reported for cats (Pypendop and Ilkiw
2008
) and humans (Grond and Sablotzki
2004
). The present study reports a higher plasmatic concentration of M2 than of M5
or M1. For the first time, a low plasma concentration of M5 has been reported. This
could be due to the remarkable glucuronidation process in camelids (Al Katheeri
et al.
2005
) that leads to a high elimination rate for M1 and M5 (as glucuronides),
without influencing M2.
Although the IV and IM routes of administration are almost bioequivalent
D
(
F
81.5%) (Toutain and Bousquet-Melou
2004
), the lower initial plasma
concentrations of tramadol following IM administration may be therapeutically
beneficial. IM administration has been suggested to have a lower incidence of side
effects with a slightly longer onset of action (Lintz et al.
1999
). Therefore,
according to the data generated in this study, IM injection of tramadol in alpacas
is a useful and better alternative to IV injection, despite the lack in the production of
M1 that could limit the analgesic effect.
ΒΌ
