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plasma

2.25 µg/mL

intestine

117 ( 6.9 µg/g

spleen

26.1 ( 1.1 µg/g

liver

26.9 ( 2.6 µg/g

kidney

7.5 ( 0.08 µg/g

brain

0.4 ( 0.01 µg/g

plasma

0.22 µg/mL

plasma

25 ( 2 nmol/mL

intestinal mucosa

200 ( 23 nmol/g

liver

73 ( 20 nmol/g

brain

2.9 ( 0.4 nmol/g

heart

9.1 ( 1.1 nmol/g

lungs

16 ( 3 nmol/g

muscle

8.4 ( 6 nmol/g

kidney

78 ( 3 nmol/g

stomach

53.3 ( 5.1 (µg/g)

small intestine

58.6 ( 11.0 (µg/g)

cecum

51.5 ( 13.5 (µg/g)

large intestine

5.1 ( 2.5 (µg/g)

serum

6.5 ( 4.5 nM

serum

0.5 µg/mL

serum

1.35 ( 0.23 µg/mL

plasma

0.06 ( 0.01 µg/mL

plasma

0.36 ( 0.05 µg/mL

serum

0.006 ( 0.005 µg /mL

serum

0.4–3.6 µM

serum

50.5 ng/m

serum

51.2 ng/mL

plasma

11.1 ( 0.6 nmol/mL

colorectum

7–20 nmol/g

mice

oral

100 mg/kg

mice

i.p.

100 mg/kg

rat

oral

340 mg/kg

rat

oral

1g/kg

rat

oral

2 g/kg

rat

oral

500 mg/kg

rat

i.v.

10 mg/kg

human

oral

2 g/kg

human

oral

4–8 g

human

oral

10 g

human

oral

12 g

human

oral

3.6 g

human

oral

0.4–3.6 g

BioaVailability of Curcumin: Problems and Promises

rat

oral

2 g/kg

a

Key: i.p., intraperitoneal; i.v., intravenous.

Table 1. Serum and Tissue Levels of Curcumin in Rodents and Human after Different Routes of Administration

levels

plasma/tissue

species

routea

dose

mice

i.p.

100 mg/kg

reviews

ref

34

35

32

39 38 28 37

28 27 26

36 42

dose of 1 g/kg in rats produced a maximum serum curcumin level of 0.5 µg/mL after 45 min of curcumin dosing.38 Similarly, Marczylo et al. also showed a maximum serum curcumin concentration of 6.5 ( 4.5 nM reached 0.5 h after oral dosing of curcumin.39 These studies clearly suggest the role of route of administration on achievable serum levels of curcumin and further indicate that the serum levels of curcumin in rats and in human are not directly comparable (see Table 1).

B2. Tissue Distribution. Uptake and distribution of curcumin in body tissues is obviously important for its biological activity, yet only a limited number of studies have addressed this issue. Ravindranath et al. showed that after oral administration of 400 mg of curcumin to rats only traces of unchanged drug were found in the liver and kidney. At 30 min, 90% of curcumin was found in the stomach and small intestine, but only 1% was present at 24 h.32 In an in vitro study, when everted sacs of rat intestine were incubated with 50–750 µg of curcumin in 10 mL of incubation medium 30–80% of the curcumin disappeared from the mucosal side

(37) Yang, K. Y.; Lin, L. C.; Tseng, T. Y.; Wang, S. C.; Tsai, T. H. Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2007, 853 (1–2), 183–9.

and no curcumin was found in the serosal fluid. Less than 3% of the curcumin was found in the tissues at the highest curcumin concentration.40 Another study evaluated the tissue distribution of curcumin using tritium-labeled drug. They found that radioactivity was detectable in blood, liver, and kidney following doses of 400, 80, or 10 mg of [3H]cur- cumin. With 400 mg, considerable amounts of radio labeled products were present in tissues 12 days after dosing. The percentage of curcumin absorbed (60–66% of the given dose) remained constant regardless of the dose indicating that administration of more curcumin does not result in higher absorption.33 That is, in rats there is a dose-dependent limitation to bioavailability.

  • (38)

    Maiti, K.; Mukherjee, K.; Gantait, A; Saha, B. P.; Mukherjee,

    • P.

      K. Curcumin–phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats. Int. J. Pharm. 2007, 330 (1–2), 155–63.

  • (39)

    Marczylo, T. H.; Verschoyle, R. D.; Cooke, D. N.; Morazzoni, P; Steward, W. P.; Gescher, A. J. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother. Pharmacol. 2007, 60 (2), 171–7.

  • (40)

    Ravindranath, V.; Chandrasekhara, N. In vitro studies on the intestinal absorption of curcumin in rats. Toxicology 1981, 20 (2–

      • 3)

        , 251–7.

VOL. 4, NO. 6 MOLECULAR PHARMACEUTICS 811

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