Arnold T H, Tackett R L, Vallner J J
Biopharm Drug Dispos. 1985 Oct-Dec;6(4):447-54. doi: 10.1002/bdd.2510060411.
The present study was conducted in order to examine the intranasal administration of verapamil and compare this route to oral and intravenous administration in a 3 way crossover protocol in five dogs. Unanesthetized, adult mongrel dogs were given verapamil intravenously (0.5 mg/kg), orally (2.5 mg/kg) and intranasally (0.75 mg/kg) with at least a 3-4 day washout period between each administration. Blood samples were collected over a 10 hour period and analyzed for verapamil using HPLC with fluorescence detection. A lead II ECG was monitored to determine the effects of verapamil on heart rate and P-R interval. Following intravenous administration, verapamil was distributed according to a two compartment model. Bioavailability (corrected for dose and elimination rate constant) following intranasal administration (36% +/- 7%) was approximately 3 fold that after oral administration (13% +/- 3%). Absorption from the nasal cavity appeared instantaneous compared to an absorption half-life of 50 +/- 6 min after oral administration. All three routes of administration resulted in significant increases in heart rate and increases in the P-R interval. Maximal P-R interval prolongation occurred after peak plasma concentrations of verapamil. The results of this study suggest that the intranasal route is a viable alternative route of administration for verapamil.
本研究旨在检测维拉帕米的鼻内给药情况，并在5只犬身上采用三向交叉试验方案将该给药途径与口服和静脉给药途径进行比较。未麻醉的成年杂种犬分别接受静脉注射（0.5 mg/kg）、口服（2.5 mg/kg）和鼻内给药（0.75 mg/kg），每次给药之间至少有3 - 4天的洗脱期。在10小时内采集血样，采用带荧光检测的高效液相色谱法分析维拉帕米。监测II导联心电图以确定维拉帕米对心率和P - R间期的影响。静脉给药后，维拉帕米按二室模型分布。鼻内给药后的生物利用度（根据剂量和消除速率常数校正）为36%±7%，约为口服给药后（13%±3%）的3倍。与口服给药后50±6分钟的吸收半衰期相比，鼻腔吸收似乎是瞬间完成的。所有三种给药途径均导致心率显著增加和P - R间期延长。维拉帕米血药浓度峰值后出现最大P - R间期延长。本研究结果表明，鼻内给药途径是维拉帕米一种可行的替代给药途径。
