Benowitz N L, Jacob P, Olsson P, Johansson C J
Clinical Pharmacology Unit of the Medical Service, San Francisco General Hospital Medical Center, University of California.
Clin Pharmacol Ther. 1992 Sep;52(3):223-30. doi: 10.1038/clpt.1992.134.
For most drugs delivered by the transdermal route, percutaneous absorption is limited by the rate of release of the drug from the device or by diffusion across the stratum corneum. However, systemic absorption also requires that the drug be taken up by dermal blood vessels. As part of a bioavailability study of a transdermal delivery system, we observed that a concomitant intravenous infusion of nicotine had a marked effect on the absorption kinetics of transdermal nicotine. Plasma concentrations of nicotine rose less rapidly, reached a lower peak, and peaked at a later time, indicating delayed absorption of transdermal nicotine after intravenous nicotine versus after transdermal nicotine administered alone. Nicotine is known to produce cutaneous vasoconstriction. The likely explanation for our observation is that intravenous nicotine constricts dermal blood vessels, thereby limiting percutaneous absorption. Other vasoconstrictor drugs would be expected to retard the absorption of transdermal nicotine and perhaps other transdermal drugs as well.
对于大多数通过透皮途径给药的药物，经皮吸收受药物从装置中释放的速率或通过角质层扩散的速率限制。然而，全身吸收还要求药物被真皮血管摄取。作为透皮给药系统生物利用度研究的一部分，我们观察到静脉输注尼古丁对透皮尼古丁的吸收动力学有显著影响。尼古丁的血浆浓度上升较慢，达到的峰值较低，且峰值出现时间较晚，这表明与单独给予透皮尼古丁相比，静脉注射尼古丁后透皮尼古丁的吸收延迟。已知尼古丁会引起皮肤血管收缩。对我们观察结果的可能解释是静脉注射尼古丁会使真皮血管收缩，从而限制经皮吸收。预计其他血管收缩药物也会延缓透皮尼古丁以及可能其他透皮药物的吸收。
