Titre du document / Document title

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

Auteur(s) / Author(s)

VAN HOOGDALEM E. J. ⁽¹⁾ ; BAVEN T. L. M. ⁽¹⁾ ; SPIEGEL-MELSEN I. ⁽¹⁾ ; TERPSTRA I. J. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Clinical Pharmacology Research Department, Yamanouchi Europe B.V., Leiderdorp, PAYS-BAS

Résumé / Abstract

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 HCI, 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.

Revue / Journal Title

Biopharmaceutics & drug disposition   ISSN 0142-2782   CODEN BDDID8 

Source / Source

1998, vol. 19, n^o9, pp. 563-569 (23 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley, Chichester, ROYAUME-UNI  (1979) (Revue)

Mots-clés anglais / English Keywords

Clindamycin ; Antibiotic ; Antibacterial agent ; Tretinoin ; Antineoplastic agent ; Retinoid ; Pharmacokinetics ; Urine ; Biological fluid ; Absorption ; Transdermal system ; Human ; Percutaneous route ; Freeze ; Pharmaceutical technology ; Comparative study ; Bioavailability ; Bioequivalence ; Skin ; Face ; Toxicity ; Secondary effect ; Elimination ;

Mots-clés français / French Keywords

Clindamycine ; Antibiotique ; Antibactérien ; Trétinoïne ; Anticancéreux ; Rétinoïde ; Pharmacocinétique ; Urine ; Liquide biologique ; Absorption ; Système transdermique ; Homme ; Voie percutanée ; Gel ; Technologie pharmaceutique ; Etude comparative ; Biodisponibilité ; Bioéquivalence ; Peau ; Face ; Toxicité ; Effet secondaire ; Elimination ;

Mots-clés espagnols / Spanish Keywords

Clindamicina ; Antibiótico ; Antibacteriano ; Tretinoína ; Anticanceroso ; Retinoide ; Farmacocinética ; Orina ; Líquido biológico ; Absorción ; Sistema transdérmico ; Hombre ; Vía percutánea ; Helada ; Tecnología farmacéutica ; Estudio comparativo ; Biodisponibilidad ; Bioequivalencia ; Piel ; Cara ; Toxicidad ; Efecto secundario ; Eliminación ;

Localisation / Location

INIST-CNRS, Cote INIST : 17959, 35400007299614.0020