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

Spinal cord injury (SCI) has been proposed to reduce drug bioavailability a fter intramuscular administration owing to an impairment in blood now to pa ralyzed limbs. To test this hypothesis, we studied diclofenac bioavailabili ty after intramuscular administration in rats with SCI. Female Sprague-Dawl ey rats were submitted to SCI at the T8 level by contusion and received a 1 0-mg/kg intramuscular diclofenac dose in the thigh of the right hind limb 2 4 h after injury. Blood samples were drawn, diclofenac concentration was de termined by high-performance liquid chromatography, and whole-blood concent ration against time curves were constructed. SCI did not result in a signif icant change in C-max and T-max compared with sham-lesioned controls, sugge sting that the rate of drug absorption was not altered. Half-life was prolo nged, and therefore area under the curve was greater in SCI than in sham-le sioned animals. Therefore, 24 h after SCI at the TS level, intramuscular di clofenac bioavailability was not impaired but was actually enhanced. Result s suggest that the rate of intramuscular diclofenac absorption is not signi ficantly altered, although its elimination is impaired, during the acute ph ase of SCI. It then appears that SCI-induced pharmacokinetic alterations ar e complex, the global bioavailability depending on the sum of SCI effects o n absorption, distribution, and elimination. Systematic studies on SCI-indu ced alterations are thus required to provide information leading to a ratio nal dosing regimen design for SCI patients. (C) 2000 Elsevier Science Inc. All rights reserved.