METOCLOPRAMIDE INCREASES THE BIOAVAILABILITY OF DANTROLENE IN SPINAL-CORD INJURY

A study was conducted to determine the effect of metoclopramide on the disposition of dantrolene in patients with spinal cord injury (SCI) a nd in neurologically intact, able-bodied volunteers. Fifteen serum sam ples each were collected from 6 able-bodied volunteers and 13 patients with SCI (7 paraplegics, 6 quadriplegics) in a prospective, open-labe l, pharmacokinetic study of a single 100-mg oral dose of dantrolene. A fter a washout period, a single 10-mg intravenous dose of metocloprami de was given along with dantrolene to the patients with SCI only, and the study was repeated in sequential, crossover fashion. Concentration s of dantrolene were measured by a high-performance liquid chromatogra phy (HPLC) assay. Numerical integration was used to calculate area und er the curve (AUC) and mean residence time (MRT). Differences were stu died using paired and two-sample, nonparametric tests, with 0.05 as th e significance level. Without metoclopramide, the AUC of dantrolene wa s larger in able-bodied volunteers than in patients with SCI, and the MRT of dantrolene was similar both groups. When patients with SCI rece ived metoclopramide before treatment with dantrolene, the median incre ase in the AUC for dantrolene was 57%, with no change in MRT. This pha rmacokinetic interaction is probably attributable to augmented absorpt ion and could alter the pharmacologic action of dantrolene. Concurrent treatment of patients with SCI with metoclopramide and dantrolene sho uld be accompanied by careful surveillance to avoid toxicity and prese rve efficacy.