Pharmacokinetic analysis of capsaicin after topical administration of a high-concentration capsaicin patch to patients with peripheral neuropathic pain

Ther Drug Monit. 2009 Aug;31(4):502-10. doi: 10.1097/FTD.0b013e3181a8b200.


Capsaicin, a pungent compound in chili peppers, is a highly selective agonist for the transient receptor potential vanilloid 1 receptor expressed in nociceptive sensory nerves. A high-concentration (640 microg/cm2) capsaicin patch, designated NGX-4010, is in clinical evaluation for the management of peripheral neuropathic pain. To determine systemic capsaicin exposure after single 60- or 90-minute NGX-4010 applications, plasma samples were collected from 173 patients with postherpetic neuralgia (PHN), painful human immunodeficiency virus-associated neuropathy (HIV-AN), and painful diabetic neuropathy (PDN). The percentages of patients with quantifiable levels of capsaicin at any time point were 31% for PHN (30 of 96), 7% for HIV-AN (3 of 44), and 3% for PDN (1 of 33). The maximum plasma concentration observed in any patient was 17.8 ng/mL. Due to the limited number of quantifiable levels, a population analysis was performed to characterize the pharmacokinetics (PK) of capsaicin. Plasma concentrations were fitted adequately using a 1-compartment model with first-order absorption and linear elimination. Capsaicin levels declined very rapidly, with a mean population elimination half-life of 1.64 hours. Mean area under the curve and C max values after a 60-minute application were 7.42 ng x h/mL and 1.86 ng/mL, respectively. Only a few correlations between calculated PK parameters and patient characteristics were observed. Duration and area of application of the patch were detected as significant covariates explaining the PK of capsaicin. Ninety-minute applications of NGX-4010 resulted in capsaicin area under the curve and Cmax values approximately 1.78- and 2.15-fold higher than those observed in patients treated for 60 minutes. Treatment on the feet (patients with HIV-AN and PDN) produced far lower systemic exposure than treatment on the trunk (patients with PHN). Finally, larger treatment areas were associated with statistically higher Vc/F values. The low systemic exposure and very rapid elimination half-life of capsaicin after NGX-4010 administration are unlikely to result in systemic effects and support the overall safety profile of this investigational cutaneous patch.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Administration, Topical
  • Capsaicin / administration & dosage
  • Capsaicin / pharmacokinetics*
  • Capsaicin / pharmacology
  • Capsicum
  • Dosage Forms
  • Dose-Response Relationship, Drug
  • Female
  • HIV Infections
  • HIV-1
  • Half-Life
  • Humans
  • Kinetics
  • Male
  • Pain / metabolism*
  • Pain Measurement
  • Peripheral Nervous System Diseases / metabolism*
  • Treatment Outcome


  • Dosage Forms
  • Capsaicin