P. Garcialopez et al., ORAL PARACETAMOL BIOAVAILABILITY IN RATS SUBJECTED TO EXPERIMENTAL SPINAL-CORD INJURY, Biopharmaceutics & drug disposition, 18(3), 1997, pp. 203-211
The purpose of the present study was to examine the time dependence of
oral paracetamol (acetaminophen) bioavailability in an experimental m
odel of spinal cord injury (SCI). Female Sprague-Dawley rats were subj
ected to spinal cord contusion at the T8-T9 level by the weight drop m
ethod producing permanent paraplegia. Oral paracetamol bioavailability
after administration of a single 100 mgkg(-1) dose was determined 1,
12, and 50d after SCI. C-max and AUC were significantly decreased id a
fter SCI compared to sham-injured controls. This reduction, however, w
as temporary, as there was a recovery of bioavailability parameters wh
ich was partial 12d after SCI, being complete by day 50. The present r
esults confirm the usefulness of animal models for the characterizatio
n of the effect of SCI in drug kinetics. Data show that SCI induces si
gnificant changes in paracetamol pharmacokinetics. Nonetheless, despit
e the fact of a permanent loss of functions related to locomotion, pha
rmacokinetic alterations evolved with time. (C) 1997 by John Wiley & S
ons, Ltd.