Transdermal absorption of clindamycin and tretinoin from topically applied anti-acne formulations in man.
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.
van Hoogdalem
E J
EJ
Clinical Pharmacology Research Department, Yamanouchi Europe B.V., Leiderdorp, The Netherlands. hoogdalem.nl@yamanouchi-eu.com
Baven
T L
TL
Spiegel-Melsen
I
I
Terpstra
I J
IJ
D000152:Acne Vulgaris / Q000188:drug therapy / Q000378:metabolism*; D000279:Administration, Cutaneous; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D002981:Clindamycin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004890:Erythema / Q000139:chemically induced; D005782:Gels; D006801:Humans; D007641:Keratolytic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D010865:Pilot Projects; D012869:Skin Absorption; D014212:Tretinoin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D005782:Gels; D007641:Keratolytic Agents; D002981:Clindamycin; D014212:Tretinoin