title: Systemic exposure to benzoic acid and hippuric acid following topical application of clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel in Japanese patients with acne vulgaris.
abstract: Clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel (CLDM/BPO3%) is a topical product for the treatment of acne vulgaris. In this study, plasma and urine concentrations of benzoic acid (BA) and hippuric acid (HA) were analyzed to estimate the pharmacokinetics (PK) of BPO after application of CLDM/BPO3% twice-daily for 7 days in Japanese patients with acne vulgaris. Seven-day repeated application of CLDM/BPO3% appears to be safe in this patient population. Concentrations of plasma and urine BA were below the limit of quantification before and after repeated application in most of the 12 adult male patients. Mean difference in Cmax and AUC0-last for plasma HA indicated increased exposures after repeated application, but with wide 90% confidence intervals. Mean Ae0-12 for urine HA was similar before and after repeated application. Repeated application of CLDM/BPO3% is thus unlikely to result in accumulation of BA and HA. The study suggests negligible systemic exposure to BPO metabolites from CLDM/BPO3% after 7-day repeated application in male patients with acne vulgaris.
authors.affiliation: GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ino
authors.affiliation: GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Stiefel, A GSK Company, Research Triangle Park, NC, USA.
authors.forename: Alessandra Alio
authors.initials: AA
authors.lastname: Saenz
authors.affiliation: GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Wakamatsu
authors.affiliation: GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Norie
authors.initials: N
authors.lastname: Nakahara
authors.affiliation: Pharmaspur, Inc., Tokyo, Japan.
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hasegawa
mesh_terms: D000152:Acne Vulgaris / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology; D000279:Administration, Cutaneous; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D019817:Benzoic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001585:Benzoyl Peroxide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001711:Biotransformation; D002981:Clindamycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods; D006626:Hippurates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D003879:Dermatologic Agents; D004338:Drug Combinations; D006626:Hippurates; C466951:clindamycin phosphate benzoyl peroxide combination; D002981:Clindamycin; D019817:Benzoic Acid; C030514:hippuric acid; D001585:Benzoyl Peroxide
keywords: acne vulgaris; benzoic acid; benzoyl peroxide; hippuric acid; pharmacokinetics