Kobayashi I, Hosaka K, Ueno T, Maruo H, Kamiyama M, Konno C, Gemba M
Toxicological Research Center, Nitto Denko Corporation, Osaka, Japan.
Biol Pharm Bull. 1997 Apr;20(4):421-7. doi: 10.1248/bpb.20.421.
We evaluated the relationship between the cumulative amounts of 5 kinds of beta-blockers (alprenolol, oxprenolol, timolol, acebutolol and atenolol) permeating through the stratum corneum and a* values obtained by measuring the formation of erythema, a skin irritation reaction, with a chromameter after transdermal application of adhesive patches containing 2 beta-blocker to the skin of guinea pigs. The cumulative amount of beta-blocker released from each adhesive patch to the skin increased with the increase in application time. The contents of alprenolol, oxprenolol and timolol in the stratum corneum and in the stripped skin increased markedly up to 4 h after application and thereafter were maintained at high levels up to 24 h. The contents of acebutolol and atenolol, on the other hand, increased up to 24 h, but these values were low. a* values of all adhesive patches 24 h after application were higher than those before application. The correlation coefficients between the cumulative amounts of alprenolol, oxprenolol, timolol, acebutolol or atenolol permeating through the stratum corneum and (delta a* -delta aPlacebo) values were 0.739, 0.717, 0.722, 0.551 and 0.633, respectively. The correlation coefficient calculated by averaging the cumulative amounts of 6 kinds of beta-blockers permeating through the stratum corneum [including propranolol which was reported previously (Kobayashi I., et al., Biol. Pharm. Bull., 19, 839-844 (1996))] was 0.731, higher than the correlation coefficient between contents of these beta-blockers in the stripped skin and (delta a -delta aPlacebo) values (r = 0.552). This suggests that there was a high correlation between the cumulative amounts of beta-blockers permeating through the stratum corneum and (delta a -delta a*Placebo) values.
我们评估了5种β受体阻滞剂(阿普洛尔、氧烯洛尔、噻吗洛尔、醋丁洛尔和阿替洛尔)透过角质层的累积量与通过对豚鼠皮肤经皮贴敷含2种β受体阻滞剂的贴剂后用色差计测量皮肤刺激反应红斑形成所获得的a值之间的关系。从每个贴剂释放到皮肤的β受体阻滞剂累积量随贴敷时间的增加而增加。阿普洛尔、氧烯洛尔和噻吗洛尔在角质层和去皮皮肤中的含量在贴敷后4小时内显著增加,此后直至24小时保持在高水平。另一方面,醋丁洛尔和阿替洛尔的含量在24小时内增加,但这些值较低。所有贴剂在贴敷24小时后的a值均高于贴敷前。阿普洛尔、氧烯洛尔、噻吗洛尔、醋丁洛尔或阿替洛尔透过角质层的累积量与(Δa* - Δa安慰剂)值之间的相关系数分别为0.739、0.717、0.722、0.551和0.633。通过平均6种β受体阻滞剂透过角质层的累积量(包括先前报道的普萘洛尔(小林一,等人,生物药剂与药代动力学,19,839 - 844(1996)))计算得到的相关系数为0.731,高于这些β受体阻滞剂在去皮皮肤中的含量与(Δa - Δa安慰剂)值之间的相关系数(r = 0.552)。这表明β受体阻滞剂透过角质层的累积量与(Δa - Δa*安慰剂)值之间存在高度相关性。