ORAL PARACETAMOL BIOAVAILABILITY IN RATS SUBJECTED TO EXPERIMENTAL SPINAL-CORD INJURY

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.