Pharmacokinetics of tramadol in rat plasma and cerebrospinal fluid after intranasal administration.

We have evaluated the potential of intranasal administration of tramadol. The pharmacokinetic behaviour of tramadol in rat plasma and cerebrospinal fluid (CSF) after intranasal administration was determined and compared with those after intravenous and oral administration. Serial plasma and CSF samples were collected for 6 h, and the drug concentrations were assayed by an HPLC-fluorescence method. The plasma absolute bioavailability values of tramadol after intranasal and oral administration were 73.8% and 32.4%, respectively, in conscious rats. The Cmax (maximum concentration) value after the intranasal dose was lower (P<0.05), and the MRT (mean retention time) was longer (P<0.05) than the values obtained after intravenous administration. A pharmacokinetic study of tramadol in plasma and CSF was undertaken in anaesthetized rats. The absolute bioavailability values in plasma and CSF after intranasal administration were 66.7% and 87.3%, respectively. The Cmax values in plasma and CSF after a nasal dose were lower (P<0.05) than after the intravenous dose. The values of Cmax and AUC0-->6 h in plasma and CSF after intranasal administration were higher than after the oral dose. The mean drug-targeting efficiency after intranasal administration was significantly greater than after the oral dose. In conclusion, intranasal administration of tramadol appeared to be a promising alternative to the traditional administration modes for this drug.