Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans

Int J Clin Pharmacol Ther. 2015 Jan;53(1):54-65. doi: 10.5414/CP202076.

Abstract

Introduction: Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects.

Material and methods: 50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study. Subjects received a single dose of liposomal curcumin (10 - 400 mg/m2; n = 2 - 6 per group) or placebo over 2 hours intravenously.

Results: Dose-dependent increases in the plasma concentrations of curcumin and its metabolite tetrahydrocurcumin (THC) were detected. After the end of drug infusion, curcumin and THC plasma concentrations decreased within 6 - 60 minutes below the limit of quantification. Mean urinary excretion was ~ 0.1% of total systemic clearance. Liposomal curcumin was tolerated well, but a transient red blood cell echinocyte formation with concomitant increase in mean cellular volume was observed at dosages ≥ 120 mg/m2.

Conclusion: Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.

Trial registration: ClinicalTrials.gov NCT01403545.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / blood
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / urine
  • Biotransformation
  • Curcumin / administration & dosage*
  • Curcumin / adverse effects
  • Curcumin / analogs & derivatives
  • Curcumin / metabolism
  • Curcumin / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Erythrocytes / drug effects
  • Erythrocytes / pathology
  • Female
  • Healthy Volunteers
  • Humans
  • Infusions, Intravenous
  • Liposomes
  • Male
  • Middle Aged
  • Renal Elimination
  • Risk Assessment
  • Young Adult

Substances

  • Antineoplastic Agents, Phytogenic
  • Liposomes
  • tetrahydrocurcumin
  • Curcumin

Associated data

  • ClinicalTrials.gov/NCT01403545
  • EudraCT/2011-001861-41