title: Pharmacokinetics of dexamethasone and nefopam administered alone or in combination using a newly developed prefilled multi-drug injector in rats.
abstract: OBJECTIVE
  It is significant for patients with traumatic brain injury (TBI) to receive prehospital emergency treatment as early as possible to reduce mortality. Therefore, a new prefilled multi-drug injector was developed to improve the treatment of TBI. Here, we studied the pharmacokinetics of dexamethasone (DXM) and nefopam using the injector to investigate the significance of drug interactions and the necessity of dose adjustment.
  
  
  METHODS
  Rats were administered DXM and nefopam intramuscularly alone or in combination using the injector. The concentrations of DXM and nefopam were measured by means of HPLC. The noncompartmental approach was used to calculate pharmacokinetic parameters.
  
  
  RESULTS
  All animals appeared to tolerate the injection very well. The maximum concentration 90% confidence interval (CI) of nefopam was in the bioequivalence range when nefopam was co-administered with DXM. However, the AUC 90% CI of nefopam was out of the range. A statistically significant alteration was also observed in the clearance of nefopam. The co-administration exhibited no significant influence on the pharmacokinetic parameters of DXM.
  
  
  CONCLUSIONS
  These results indicate that the co-administration of DXM and nefopam using the prefilled multi-drug injector significantly alters some pharmacokinetic parameters of nefopam and has a minor effect on DXM pharmacokinetics.
authors.affiliation: College of Materials Science and Engineering, Sichuan University, Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Junhai
authors.initials: J
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Kaihua
authors.initials: K
authors.lastname: Fan
authors.forename: Jianwen
authors.initials: J
authors.lastname: Gu
authors.forename: Guangfu
authors.initials: G
authors.lastname: Yin
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D003907:Dexamethasone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005938:Glucocorticoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007273:Injections, Intramuscular; D008297:Male; D009340:Nefopam / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D009340:Nefopam; D003907:Dexamethasone