title: Metoclopramide increases the bioavailability of dantrolene in spinal cord injury.
abstract: A study was conducted to determine the effect of metoclopramide on the disposition of dantrolene in patients with spinal cord injury (SCI) and in neurologically intact, able-bodied volunteers. Fifteen serum samples each were collected from 6 able-bodied volunteers and 13 patients with SCI (7 paraplegics, 6 quadriplegics) in a prospective, open-label, pharmacokinetic study of a single 100-mg oral dose of dantrolene. After a washout period, a single 10-mg intravenous dose of metoclopramide was given along with dantrolene to the patients with SCI only, and the study was repeated in sequential, crossover fashion. Concentrations of dantrolene were measured by a high-performance liquid chromatography (HPLC) assay. Numerical integration was used to calculate area under the curve (AUC) and mean residence time (MRT). Differences were studied using paired and two-sample, nonparametric tests, with 0.05 as the significance level. Without metoclopramide, the AUC of dantrolene was larger in able-bodied volunteers than in patients with SCI, and the MRT of dantrolene was similar both groups. When patients with SCI received metoclopramide before treatment with dantrolene, the median increase in the AUC for dantrolene was 57%, with no change in MRT. This pharmacokinetic interaction is probably attributable to augmented absorption and could alter the pharmacologic action of dantrolene. Concurrent treatment of patients with SCI with metoclopramide and dantrolene should be accompanied by careful surveillance to avoid toxicity and preserve efficacy.
authors.affiliation: University of Southern California, School of Pharmacy, Los Angeles, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Gilman
authors.forename: J L
authors.initials: JL
authors.lastname: Segal
authors.forename: S R
authors.initials: SR
authors.lastname: Brunnemann
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D003620:Dantrolene / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010264:Paraplegia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D011446:Prospective Studies; D011782:Quadriplegia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D012016:Reference Values; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D018492:Dopamine Antagonists; D009125:Muscle Relaxants, Central; D003620:Dantrolene; D008787:Metoclopramide