Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans

• Published in: International journal of clinical pharmacology and therapeutics Vol. 53; no. 1; p. 54
• Main Authors: Storka, Angela, Vcelar, Brigitta, Klickovic, Uros, Gouya, Ghazaleh, Weisshaar, Stefan, Aschauer, Stefan, Bolger, Gordon, Helson, Lawrence, Wolzt, Michael
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2015
• Subjects: 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
• ISSN: 0946-1965
• DOI: 10.5414/cp202076

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. 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. 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. 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.