Both geniposide (Ge) and natural borneol (NB) are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography (HPLC) after intranasal administration of Ge (4 mg/kg) alone and combined with different doses (0.08, 0.8, and 8 mg/kg) of NB. The intravenous administration was given as a reference (4 mg/kg of Ge and 8 mg/kg of NB). Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter (3-5 min vs. 40 min); the peak concentration became higher (1.32-4.25 μg/ml vs. 0.67 μg/ml); and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.
Yang LUShou-ying DUXiao-lan CHENQing WUXiao SONGBing XUYong-song ZHAI
Borneol,a monoterpenoid alcohol,is used widely,particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine.In order to understand the blood and brain pharmacokinetics after intravenous,intranasal,or oral administration and to investigate the superiority and feasibility of intranasal administration,a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol.Blood samples and brain were collected from mice at 1,3,5,10,20,30,60,90,and 120 min after intravenous,intranasal,or oral administration of borneol at a dosage of 30.0 mg/kg.Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane.The pharmacokinetic parameters were calculated by the software of Kinetica.The calibration curves were linear in the range of 0.11-84.24 μg/ml and 0.16-63.18 μg/g for borneol in plasma and brain,respectively.The methodological and extraction recoveries were both in the range of 85%-115%.The intra-day and inter-day variabilities for plasma and brain samples were ≤5.00% relative standard deviation (RSD).The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%.The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%.The GC-FID method developed could be applied to determination and pharmacokinetic study.The borneol from injection was distributed and metabolized fast without absorption process.The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability.Nasal administration of borneol was quickly absorbed into the blood and brain,was easy to use and had a greater safety than infection,which makes it worthy of further development as an administration route for encephalopathy treatment.
Jing-yi ZHAOYang LUShou-ying DUXiao SONGJie BAIYue WANG
