title: Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Angela
authors.initials: A
authors.lastname: Storka
authors.forename: Brigitta
authors.initials: B
authors.lastname: Vcelar
authors.forename: Uros
authors.initials: U
authors.lastname: Klickovic
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Gouya
authors.forename: Stefan
authors.initials: S
authors.lastname: Weisshaar
authors.forename: Stefan
authors.initials: S
authors.lastname: Aschauer
authors.forename: Gordon
authors.initials: G
authors.lastname: Bolger
authors.forename: Lawrence
authors.initials: L
authors.lastname: Helson
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D000293:Adolescent; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D003474:Curcumin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D065667:Renal Elimination; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; C096277:tetrahydrocurcumin; D003474:Curcumin