Compatibility and stability of binary mixtures of acetaminophen, nefopam, ketoprofen and ketamine in infusion solutions

Eur J Anaesthesiol. 2009 Jan;26(1):23-7. doi: 10.1097/EJA.0b013e328319c04b.


Background and objective: Administering various combinations of acetaminophen, ketoprofen, nefopam and ketamine, though sometimes discussed, is expected to provide superior pain relief and reduce opioid analgesic-related side effects. However, some studies have indicated that multimodal analgesia has limited efficacy. We studied the stability of various binary combinations of these four drugs.

Patients and methods: The drugs were studied at 25 degrees C. Binary mixtures of acetaminophen, ketoprofen, nefopam and ketamine were produced. Each drug concentration was assessed using a specific high-performance liquid chromatographic technique. Measurements were carried out at T0, +1, +2, +4, +6 and +24 h. A 5% loss of initial concentration was considered to be significant. The changes with time of the concentrations were analysed using linear regression analysis. A P value of less than 0.05 was significant.

Results: The four drugs tested in the binary mixtures were stable, showing neither loss of concentration nor degradation products (P > or = 0.05).

Conclusion: Physicochemical negative interaction is not likely to account for the limited clinical efficacy sometimes reported with binary combinations of these drugs. Coadministration of binary mixtures of acetaminophen, nefopam, ketoprofen and ketamine from the same bottle or infusion bag using the same venous line is demonstrated to be feasible.

MeSH terms

  • Acetaminophen / analysis*
  • Humans
  • Ketamine / analysis*
  • Ketoprofen / analysis*
  • Nefopam / analysis*
  • Solutions


  • Solutions
  • Acetaminophen
  • Nefopam
  • Ketamine
  • Ketoprofen