| Título: | Pharmacokinetics of a Cytochrome P450 2E1 Probe, Chlorzoxazone, and its 6-Hydroxy Metabolite in Poloxamer 407-Induced Hyperlipidemic Rats |
| Autores: |
Kwon, Mi Hye; College of Pharmacy, The Catholic University of Korea Lee, Cheol Jung; College of Pharmacy, The Catholic University of Korea Cho, Yong Yeon; College of Pharmacy, The Catholic University of Korea Kang, Hee Eun; College of Pharmacy, The Catholic University of Korea |
| Fecha: | 2013-11-06 |
| Publicador: | Journal of Pharmacy and Pharmaceutical Sciences |
| Fuente: |
 |
| Tipo: |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| Tema: | No aplica |
| Descripción: | Purpose. To evaluate the possible changes in CYP2E1 expression and activity in hyperlipidemia (HL), we evaluated the pharmacokinetics of chlorzoxazone (CZX) as a CYP2E1 probe in rats with HL induced by poloxamer 407 (HL rats). Methods. The pharmacokinetics of CZX and its 6-hydroxy metabolite (OH-CZX) were evaluated after intravenous administration of 20 mg/kg CZX to both control and HL rats. We also examined changes in the expression of CYP2E1 and its in vitro metabolic activity in hepatic microsomal fractions from HL rats. Results. The total area under the plasma concentration–time curve (AUC) of CZX in the HL rats after its intravenous administration was comparable with that in the controls due to unchanged non-renal clearance (CLNR). The AUC of OH-CZX and AUCOH-CZX/AUCCZX ratios in HL rats also remained unchanged. This was primarily due to the comparable hepatic CLint for metabolism of CZX to OH-CZX via CYP2E1 between the control and HL rats as a result of unchanged expression of CYP2E1 in HL rats. Conclusions. This is the first study to evaluate CYP2E1 expression and activity in HL rats and their effects on the pharmacokinetics of a CYP2E1 probe drug. These findings have potential therapeutic implications assuming that the HL rat model qualitatively reflects similar changes in patients with HL. |
| Idioma: | Inglés |
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