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

Clin Pharmacol Drug Dev. 2015 Jan;4(1):18-24. doi: 10.1002/cpdd.125. Epub 2014 Jun 9.

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.

Keywords: acne vulgaris; benzoic acid; benzoyl peroxide; hippuric acid; pharmacokinetics.

Publication types

  • Clinical Trial

MeSH terms

  • Acne Vulgaris / blood
  • Acne Vulgaris / diagnosis
  • Acne Vulgaris / drug therapy*
  • Acne Vulgaris / ethnology
  • Administration, Cutaneous
  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Asian People
  • Benzoic Acid / blood
  • Benzoic Acid / pharmacokinetics*
  • Benzoic Acid / urine
  • Benzoyl Peroxide / administration & dosage*
  • Benzoyl Peroxide / adverse effects
  • Benzoyl Peroxide / pharmacokinetics*
  • Biotransformation
  • Clindamycin / administration & dosage*
  • Clindamycin / adverse effects
  • Clindamycin / pharmacokinetics*
  • Dermatologic Agents / administration & dosage*
  • Dermatologic Agents / adverse effects
  • Dermatologic Agents / pharmacokinetics*
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Monitoring / methods
  • Hippurates / blood
  • Hippurates / pharmacokinetics*
  • Hippurates / urine
  • Humans
  • Japan
  • Male
  • Metabolic Clearance Rate
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Dermatologic Agents
  • Drug Combinations
  • Hippurates
  • clindamycin phosphate benzoyl peroxide combination
  • Clindamycin
  • Benzoic Acid
  • hippuric acid
  • Benzoyl Peroxide