Bioavailability of diclofenac after intramuscular administration to rats with experimental spinal cord injury.

Spinal cord injury (SCI) has been proposed to reduce drug bioavailability after intramuscular administration owing to an impairment in blood flow to paralyzed limbs. To test this hypothesis, we studied diclofenac bioavailability after intramuscular administration in rats with SCI. Female Sprague-Dawley rats were submitted to SCI at the T8 level by contusion and received a 10-mg/kg intramuscular diclofenac dose in the thigh of the right hind limb 24 h after injury. Blood samples were drawn, diclofenac concentration was determined by high-performance liquid chromatography, and whole-blood concentration against time curves were constructed. SCI did not result in a significant change in C(max) and T(max), compared with sham-lesioned controls, suggesting that the rate of drug absorption was not altered. Half-life was prolonged, and therefore area under the curve was greater in SCI than in sham-lesioned animals. Therefore, 24 h after SCI at the T8 level, intramuscular diclofenac bioavailability was not impaired but was actually enhanced. Results suggest that the rate of intramuscular diclofenac absorption is not significantly altered, although its elimination is impaired, during the acute phase of SCI. It then appears that SCI-induced pharmacokinetic alterations are complex, the global bioavailability depending on the sum of SCI effects on absorption, distribution, and elimination. Systematic studies on SCI-induced alterations are thus required to provide information leading to a rational dosing regimen design for SCI patients.