Uptake and elimination of methylprednisolone from contused cat spinal cord following intravenous injection of the sodium succinate ester

The uptake and elimination of methylprednisolone by the injured spinal cord were examined following a single 30-mg/kg intravenous bolus injection of the sodium succinate ester. The findings were considerably different from those previously reported for normal lumbar cord. When the glucocorticoid was administered 30 minutes after a 400 gm-cm contusion injury, peak tissue concentrations in both injured and uninjured segments of traumatized spinal cord were not achieved until 30 minutes following drug administration. The elimination of methylprednisolone from injured spinal cord tissue was biphasic in nature, with a rapid elimination phase occurring between 1 and 2 hours after drug administration. This rapid elimination phase was followed by a slower phase which paralleled the constant elimination rate from uninjured tissue of traumatized cord (approximate half-time = 6 hours). Significantly more methylprednisolone accumulated in the injured segment of traumatized spinal cord than in an uninjured segment adjacent to the injury site. This was only true, however, if the drug was administered at times up to 1 hour after injury. If injected after 1 hour, uptake by the injured segment decreased significantly with time after trauma and was no different from that observed for the uninjured segment in the same animal, which showed no significant variation with time after trauma. The probable basis for these differences and the possible clinical implications of these pharmacokinetic characteristics are discussed.