Abstract
Goals were to evaluate indomethacin ethyl ester-nanoencapsules (IndOEt-NC) pharmacokinetics in rats and the in vivo ester conversion to indomethacin (IndOH). After i.v. and oral administration exclusively IndOH was detected in plasma. The AUC(IndOEt-NC)/AUC(IndOH) ratio after i.v. dosing was 0.68, accounting for dose and molecular weight differences, probably due to increased IndOH clearance after IndOEt-NC administration (alpha=0.05). The results confirm that antiedematogenic activity reported for IndOEt-NC is due to IndOH. Encapsulation did not protect the ester which in vivo is rapidly released and converted to IndOH, acting as a pro-drug.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
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Biotransformation
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Drug Compounding
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Indomethacin / administration & dosage
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Indomethacin / analogs & derivatives*
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Indomethacin / chemistry
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Indomethacin / pharmacokinetics
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Injections, Intravenous
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Male
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Models, Biological
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Nanocapsules*
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Prodrugs / administration & dosage
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Prodrugs / chemistry
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Prodrugs / pharmacokinetics*
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Rats
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Rats, Wistar
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Nanocapsules
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Prodrugs
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indomethacin ethyl ester
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Indomethacin