Pharmacokinetic Modeling of Absorption Behavior of 9-Aminocamptothecin (9-AC) Released from Colon-specific HPMA Copolymer–9-AC Conjugate in Rats
| Autor: | Jindřich Kopeček, C. Matthew Peterson, Song Qi Gao, Pavla Kopečková, Yongen Sun |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Colon Pharmaceutical Science Absorption (skin) Pharmacology Article Intestinal absorption chemistry.chemical_compound Drug Delivery Systems Pharmacokinetics Oral administration medicine Animals Methacrylamide Pharmacology (medical) Anesthetics Local Rats Wistar Gastrointestinal Transit Cecum Models Statistical Organic Chemistry Lidocaine Antineoplastic Agents Phytogenic Rats Intestinal Absorption Liver chemistry Injections Intravenous Methacrylates Molecular Medicine Camptothecin Indicators and Reagents Aminocamptothecin Algorithms Protein Binding Biotechnology medicine.drug Conjugate |
| Zdroj: | Pharmaceutical Research. 25:218-226 |
| ISSN: | 1573-904X 0724-8741 |
| Popis: | To quantitate and predict colon-specific 9-aminocamptothecin (9-AC) release from the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-9-AC conjugate and its absorption behavior after oral administration in rats.Drug distribution in the gastrointestinal (GI) tract and the plasma concentration-time profile of 9-AC released from the HPMA copolymer conjugate were predicted using the degradation, transit, and absorption rate constants in cecum. The fate of 9-AC in cecum and liver was measured by in-situ cecum absorption and liver perfusion.Following oral administration of the conjugate, 9-AC was released rapidly in cecum. Based on the pharmacokinetic model, up to 60% of the dose was in the cecum at ~6 h, and 7% of the dose still remained there at 24 h. The predicted plasma concentration curve for released 9-AC after an oral dose of 3 mg/kg of 9-AC equivalent increased gradually and reached a peak of 98 nM at 7 h, then started decreasing slowly to 16 nM at 24 h. The bioavailability value was estimated as 0.31 after the first-pass elimination.A pharmacokinetic model delineated the impact of GI transit, drug absorption rate, and first-pass metabolism on drug disposition following oral administration of HPMA copolymer-9-AC conjugate in rats. |
| Databáze: | OpenAIRE |
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