Transdermal absorption of clindamycin and tretinoin from topically appliedanti-acne formulations in man

The percutaneous absorption of clindamycin was studied in healthy male volu nteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w /v) gels, containing clindamycin phosphate ester and clindamycin HCl, respe ctively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalaci n T(R)). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visuall y, and blood and urine were collected. Clindamycin plasma levels did not ex ceed the limit of quantification (5 ng mL(-1)) with the clindamycin phospha te formulations, but one volunteer who received the clindamycin HCl/tretino in gel showed plasma levels of up to 13 ng mL(-1). Clindamycin urinary excr etion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamy cin HCl/tretinoin gel gave significantly higher values. Erythema appeared t o be associated with increased urinary excretion The formulations were tole rated well. In a separate clinical pilot study in acne patients, the transd ermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tr etinoin gel was monitored. Plasma samples were collected after 4 and 12 wee ks of daily treatment. None of the study plasma samples contained measurabl e tretinoin levels. Clindamycin levels were not quantifiable in the majorit y (87%) of samples, the highest plasma level was II ng mL(-1). The chemical form of clindamycin proved to modulate skin irritation and percutaneous up take of clindamycin from a gel formulation in healthy subjects. There was n o indications for a notable transdermal uptake of tretinoin during daily ap plication of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake. (C) 1998 John Wiley & Sons, Ltd.