Pharmacokinetics of Curcumin Diethyl Disuccinate, a Prodrug of Curcumin, in Wistar Rats
| Autor: | Pasarapa Towiwat, Phisit Khemawoot, Chuleeporn Kittiviriyakul, Kunan Bangphumi, Pornchai Rojsitthisak |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Curcumin Metabolic Clearance Rate Metabolite Glucuronidation Administration Oral Biological Availability Pharmacology Urine 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound First pass effect Feces 0302 clinical medicine Glucuronides Pharmacokinetics Drug Stability Intestinal Elimination Medicine Animals Pharmacology (medical) Prodrugs Tissue Distribution Rats Wistar Enterohepatic circulation Biotransformation Dose-Response Relationship Drug business.industry Hydrolysis Succinates Prodrug Analgesics Non-Narcotic Bioavailability Hepatobiliary Elimination 030104 developmental biology chemistry Solubility Injections Intravenous business Half-Life |
| Zdroj: | European journal of drug metabolism and pharmacokinetics. 41(6) |
| ISSN: | 2107-0180 |
| Popis: | Curcumin is the major bioactive component of turmeric, but has poor oral bioavailability that limits its clinical applications. To improve the in vitro solubility and alkaline stability, we developed a prodrug of curcumin by succinylation to obtain curcumin diethyl disuccinate, with the goal of improving the oral bioavailability of curcumin. The in vivo pharmacokinetic profile of curcumin diethyl disuccinate was compared with that of curcumin in male Wistar rats. Doses of curcumin 20 mg/kg intravenous or 40 mg/kg oral were used as standard regimens for comparison with the prodrug at equivalent doses in healthy adult rats. Blood, tissues, urine, and faeces were collected from time zero to 48 h after dosing to determine the prodrug level, curcumin level and a major metabolite by liquid chromatography-tandem spectrometry. The absolute oral bioavailability of curcumin diethyl disuccinate was not significantly improved compared with curcumin, with both compounds having oral bioavailability of curcumin less than 1 %. The major metabolic pathway of the prodrug was rapid hydrolysis to obtain curcumin, followed by glucuronidation. Interestingly, curcumin diethyl disuccinate gave superior tissue distribution with higher tissue to plasma ratio of curcumin and curcumin glucuronide in several organs after intravenous dosing at 1 and 4 h. The primary elimination route of curcumin glucuronide occurred via biliary and faecal excretion, with evidence of an entry into the enterohepatic circulation. Curcumin diethyl disuccinate did not significantly improve the oral bioavailability of curcumin due to first pass metabolism in the gastrointestinal tract. Further studies on reduction of first pass metabolism are required to optimise delivery of curcumin using a prodrug approach. |
| Databáze: | OpenAIRE |
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