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新生恒河猴经皮吸收睾酮的研究:与成年恒河猴的比较。

Percutaneous absorption of testosterone in the newborn rhesus monkey: comparison to the adult.

作者信息

Wester R C, Noonan P K, Cole M P, Maibach H I

出版信息

Pediatr Res. 1977 Jun;11(6):737-9. doi: 10.1203/00006450-197706000-00008.

Abstract

Percutaneous absorption of testosterone was determined in newborn rhesus monkeys, an animal model which is relevant to man. Mean percentage of absorptions of 4 and 40 microng/cm2 in the newborn were, respectively, 22.5 +/- 2.2 (SD) and 6.8 +/- 2.1. Statistical comparisons (Student's t-test) of these results with those obtained with adults show no significant difference (P greater than 0.05) in skin penetration of testosternoe in newborn and adult rhesus monkeys. In the newborn, the efficiency of absorption (percentage) decreased when the topical dose was increased 10-fold. However, the total compound absorbed per cm2 area of skin actually increased from 0.9 to 2.7 microng. With one other newborn rhesus, a topical dose of 40 microng/cm2 was applied to the ventral forearm and the area was occluded for 24 hr. Percutaneous absorption was 14.7%, a value twice that from nonoccluded absorption. Systemic absorption from a topical dose becomes critical in the newborn because the ratio of surface area (cm2) to body weight (kilograms) in the newborn is 3 times that in the adult. Given equal application area of skin per newborn and adult, the systemic absorption in the newborn becomes 3 times that of the adult when based on kilograms body weight. With a different ratio of skin surfact to body weight, the therapeutic ratio probably is lower in the newborn than in the adult when the compound is applied topically.

摘要

在新生恒河猴(一种与人类相关的动物模型)中测定了睾酮的经皮吸收情况。新生猴中4微克/平方厘米和40微克/平方厘米的平均吸收百分比分别为22.5±2.2(标准差)和6.8±2.1。将这些结果与成年猴的结果进行统计学比较(学生t检验),结果显示新生猴和成年恒河猴在睾酮的皮肤渗透方面无显著差异(P>0.05)。在新生猴中,当局部剂量增加10倍时,吸收效率(百分比)降低。然而,每平方厘米皮肤实际吸收的化合物总量实际上从0.9微克增加到了2.7微克。对另一只新生恒河猴,将40微克/平方厘米的局部剂量涂于前臂腹侧,并将该区域封闭24小时。经皮吸收为14.7%,该值是非封闭吸收值的两倍。新生猴局部给药后的全身吸收变得至关重要,因为新生猴的表面积(平方厘米)与体重(千克)之比是成年猴的3倍。若新生猴和成年猴的皮肤给药面积相等,基于千克体重计算,新生猴的全身吸收量将是成年猴的3倍。由于皮肤表面积与体重的比例不同,当局部应用化合物时,新生猴的治疗指数可能低于成年猴。

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