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Transport characteristics of 9-nitrocamptothecin in the human intestinal cell line Caco-2 and everted gut sacs.
Int J Pharm. 2004 Mar 19; 272(1-2):161-71.IJ

Abstract

The intestinal absorptive characteristics and the efflux mechanisms of 9-nitrocamptothecin (9-NC), a novel water-insoluble camptothecin (CPT) derivative, were investigated. The Caco-2 cells and the everted gut sacs were used as models of the intestinal mucosa to assess transepithelial transport of 9-NC. The determination of 9-NC was performed by HPLC. In the Caco-2 cells, the absorptive transport of 9-NC was pH dependent and the transport was enhanced at weakly acidic pH on the apical side. No concentration dependence and saturation were observed for the absorptive transport of 9-NC at concentrations up to 250 microM, while secretory transport were concentration dependent and saturable process (K(m) was 49.8 +/- 1.2 microM, V(max) was 38.28 +/- 0.8 ng/cm(2)/min). In the presence of verapamil (100 microM) and CsA (10 microM), potent inhibitors of P-glyprotein (P-gp)/MRP2 (cMOAT), the P(appBL-AP)/P(appAP-BL) ratio was decreased from 3.4 to 1.4 and 1.3, respectively, and permeation of apical to basolateral was enhanced approximately two-fold. In the everted gut sacs, the absorption of 9-NC was passive diffusion and had no significant difference in different gut regions. Adding verapamil in the everted gut sacs over a concentration ranging from 10 to 100 microM, the absorption of 9-NC was significantly enhanced, especially more markedly in lower small intestine (P < 0.05). Overall, the current study suggests that pH and efflux transporters are capable of mediating the absorption and efflux of 9-NC, and they may play significant roles in limiting the oral absorption of 9-NC.

Authors+Show Affiliations

Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, PR China.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15019079

Citation

Sha, Xianyi, and Xiaoling Fang. "Transport Characteristics of 9-nitrocamptothecin in the Human Intestinal Cell Line Caco-2 and Everted Gut Sacs." International Journal of Pharmaceutics, vol. 272, no. 1-2, 2004, pp. 161-71.
Sha X, Fang X. Transport characteristics of 9-nitrocamptothecin in the human intestinal cell line Caco-2 and everted gut sacs. Int J Pharm. 2004;272(1-2):161-71.
Sha, X., & Fang, X. (2004). Transport characteristics of 9-nitrocamptothecin in the human intestinal cell line Caco-2 and everted gut sacs. International Journal of Pharmaceutics, 272(1-2), 161-71.
Sha X, Fang X. Transport Characteristics of 9-nitrocamptothecin in the Human Intestinal Cell Line Caco-2 and Everted Gut Sacs. Int J Pharm. 2004 Mar 19;272(1-2):161-71. PubMed PMID: 15019079.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transport characteristics of 9-nitrocamptothecin in the human intestinal cell line Caco-2 and everted gut sacs. AU - Sha,Xianyi, AU - Fang,Xiaoling, PY - 2003/09/10/received PY - 2003/12/05/revised PY - 2003/12/09/accepted PY - 2004/3/17/pubmed PY - 2004/7/29/medline PY - 2004/3/17/entrez SP - 161 EP - 71 JF - International journal of pharmaceutics JO - Int J Pharm VL - 272 IS - 1-2 N2 - The intestinal absorptive characteristics and the efflux mechanisms of 9-nitrocamptothecin (9-NC), a novel water-insoluble camptothecin (CPT) derivative, were investigated. The Caco-2 cells and the everted gut sacs were used as models of the intestinal mucosa to assess transepithelial transport of 9-NC. The determination of 9-NC was performed by HPLC. In the Caco-2 cells, the absorptive transport of 9-NC was pH dependent and the transport was enhanced at weakly acidic pH on the apical side. No concentration dependence and saturation were observed for the absorptive transport of 9-NC at concentrations up to 250 microM, while secretory transport were concentration dependent and saturable process (K(m) was 49.8 +/- 1.2 microM, V(max) was 38.28 +/- 0.8 ng/cm(2)/min). In the presence of verapamil (100 microM) and CsA (10 microM), potent inhibitors of P-glyprotein (P-gp)/MRP2 (cMOAT), the P(appBL-AP)/P(appAP-BL) ratio was decreased from 3.4 to 1.4 and 1.3, respectively, and permeation of apical to basolateral was enhanced approximately two-fold. In the everted gut sacs, the absorption of 9-NC was passive diffusion and had no significant difference in different gut regions. Adding verapamil in the everted gut sacs over a concentration ranging from 10 to 100 microM, the absorption of 9-NC was significantly enhanced, especially more markedly in lower small intestine (P < 0.05). Overall, the current study suggests that pH and efflux transporters are capable of mediating the absorption and efflux of 9-NC, and they may play significant roles in limiting the oral absorption of 9-NC. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/15019079/Transport_characteristics_of_9_nitrocamptothecin_in_the_human_intestinal_cell_line_Caco_2_and_everted_gut_sacs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378517304000080 DB - PRIME DP - Unbound Medicine ER -