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Anand et al.

Figure 2. Bioavailability of curcumin in rodents and man. A. Bioavailability of curcumin in mice. Curcumin (1 g/kg) was administered to mice by gavage. The mice were sacrificed 1 h later by euthanasia, the blood was collected by heart puncture, and the serum was separated by centrifugation at 14000 rpm for 2 min. The physical appearance and the HPLC profiles of serum are depicted in the figure. Oral administration of curcumin leads to its appearance in the serum of mice after just 1 h. LC/MS/MS method for the detection and quantification of free curcumin in mouse serum was performed, and the amount of free curcumin detected in the serum from curcumin treated mice fell below the limit of quantification (5 ng/mL). B. Bioavailability of curcumin in human with and without piperine. Six healthy adult male human volunteers took 2 g of curcumin with or without 5 mg of piperine (as bioperine) in a cross-over design study. Three people were randomized to receive curcumin only, while the remaining three received the curcumin + piperine combination. One week following initial drug administration, volunteers were crossed over to the opposite therapies, and blood samples were again obtained for evaluation. Plasma samples were digested with combined glucuronidase

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    sulfatase to release curcumin from conjugated forms. Curcumin levels (determined by a validated LC/MS/MS

assay) are thus reported as “total” curcumin (free drug plus drug released from conjugate forms) per milliliter of plasma. Piperine-enhanced absorption of curcumin produced a near doubling of area under the curve (AUC) (8.44 h · ng/mL for curcumin vs 15.55 h · ng/mL for curcumin + piperine). C. Turmeric oil (turmerne) enhances bioavailability of curcumin. Biocurcumax is curcumin mixed with turmeric oil. AUC was 7–8× higher when curcumin was combined with turmeric oil. For more information, visit (http://www.arjunanatural.com/HTML/biocurcumax.htm).

dietary curcumin or single doses of radiolabeled curcumin given via i.p. route35 and showed that irrespective of the dose, traces of curcumin were present in the plasma which were at levels near the limit of detection (5 pmol/mL). Animal studies conducted in our own group showed detectable amounts of curcumin (as shown by the HPLC profiles) in serum collected from curcumin-treated nude mice, just after 1 h of treatment, as opposed to that from untreated animals (unpublished data; Figure 2a). In contrast to rodents, oral dosing of 4–8 g of curcumin in humans showed peak plasma

levels of 0.41–1.75 µM after 1 h of dosing.27 Similarly, in a human clinical trial, 3.6 g of curcumin via oral route was found to produce a plasma curcumin level of 11.1 nmol/L after an hour of dosing.36

A very recent study by Yang et al. showed that 10 mg/kg of curcumin given i.v. in rats gave a maximum serum curcumin level of 0.36 ( 0.05 µg/mL, whereas a 50-fold higher curcumin dose administered orally gave only 0.06 ( 0.01 µg/mL maximum serum level in rat.37 An oral curcumin

(35) Perkins, S; Verschoyle, R. D.; Hill, K.; Parveen, I.; Threadgill, M. D.; Sharma, R. A.; Williams, M. L.; Steward, W. P.; Gescher, A. J. Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Cancer Epidemiol. Biomarkers PreV. 2002, 11 (6), 535–40.

(36) Sharma, R. A.; Euden, S. A.; Platton, S. L.; Cooke, D. N.; Shafayat, A; Hewitt, H. R.; Marczylo, T. H.; Morgan, B.; Hemingway, D.; Plummer, S. M.; Pirmohamed, M; Gescher, A. J.; Steward, W. P. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin. Cancer Res. 2004, 10 (20), 6847–54.

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MOLECULAR PHARMACEUTICS VOL. 4, NO. 6

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