van Hoogdalem E J, Baven T L, Spiegel-Melsen I, Terpstra I J
Clinical Pharmacology Research Department, Yamanouchi Europe B.V., Leiderdorp, The Netherlands.
Biopharm Drug Dispos. 1998 Dec;19(9):563-9. doi: 10.1002/(sici)1099-081x(199812)19:9<563::aid-bdd134>3.0.co;2-e.
The percutaneous absorption of clindamycin was studied in healthy male volunteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w/v) gels, containing clindamycin phosphate ester and clindamycin HCl, respectively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalacin T). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visually, and blood and urine were collected. Clindamycin plasma levels did not exceed the limit of quantification (5 ng mL(-1)) with the clindamycin phosphate formulations, but one volunteer who received the clindamycin HCl/tretinoin gel showed plasma levels of up to 13 ng mL(-1). Clindamycin urinary excretion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamycin HCl/tretinoin gel gave significantly higher values. Erythema appeared to be associated with increased urinary excretion. The formulations were tolerated well. In a separate clinical pilot study in acne patients, the transdermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tretinoin gel was monitored. Plasma samples were collected after 4 and 12 weeks of daily treatment. None of the study plasma samples contained measurable tretinoin levels. Clindamycin levels were not quantifiable in the majority (87%) of samples, the highest plasma level was 11 ng mL(-1). The chemical form of clindamycin proved to modulate skin irritation and percutaneous uptake of clindamycin from a gel formulation in healthy subjects. There was no indications for a notable transdermal uptake of tretinoin during daily application of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake.
在健康男性志愿者中研究了克林霉素的经皮吸收情况，将两种研究用的克林霉素（重量/体积百分比）/维甲酸（0.025%重量/体积）凝胶进行比较，这两种凝胶分别含有磷酸克林霉素酯和盐酸克林霉素，相对于一种克林霉素磷酸酯洗剂（1%克林霉素；达力霉素T）。根据平衡完全区组设计，将制剂每日涂于面部，持续5天。通过肉眼对皮肤发红情况进行评分，并采集血液和尿液样本。使用磷酸克林霉素制剂时，克林霉素血浆水平未超过定量限（5 ng mL⁻¹），但一名接受盐酸克林霉素/维甲酸凝胶的志愿者血浆水平高达13 ng mL⁻¹。应用磷酸克林霉素/维甲酸凝胶后12小时的克林霉素尿排泄量与参比洗剂的值相当，但盐酸克林霉素/维甲酸凝胶的值明显更高。红斑似乎与尿排泄增加有关。这些制剂耐受性良好。在一项针对痤疮患者的单独临床预试验研究中，监测了磷酸克林霉素/维甲酸凝胶中维甲酸和克林霉素的经皮吸收情况。在每日治疗4周和12周后采集血浆样本。所有研究血浆样本中均未检测到可测量的维甲酸水平。大多数（87%）样本中的克林霉素水平无法定量，最高血浆水平为11 ng mL⁻¹。事实证明，克林霉素的化学形式可调节健康受试者皮肤的刺激性以及从凝胶制剂中的经皮吸收情况。在患者每日使用凝胶期间，没有迹象表明维甲酸有明显的经皮吸收，也没有迹象表明维甲酸对克林霉素的吸收有增强作用。
