interactions of tenofovir, lamivudine, abacavir and didanosine in primary human cells交互的泰诺福韦,拉米夫定,abacavir主人体细胞和必要.pdfVIP

Pharmaceutics 2011, 3, 326-337; doi:10.3390/pharmaceutics3020326 OPEN ACCESS pharmaceutics ISSN 1999-4923 /journal/pharmaceutics Article Interactions of Tenofovir, Lamivudine, Abacavir and Didanosine in Primary Human Cells Omar Janneh 1,2,* and Saye H. Khoo 2 1 Department of Biomolecular and Sport Sciences, Coventry University, Priory Street, Coventry CV1 5FB, UK 2 Department of Pharmacology and Therapeutics, The University of Liverpool, 70, Pembroke Place, Block H, First Floor, Liverpool. L69 3GF, UK * Authors to whom correspondence should be addressed; E-Mail: o.janneh@coventry.ac.uk; Tel.: +44 (0) 2476888632; Fax: +44 (0) 2476888778. Received: 26 May 2011; in revised form: 8 June 2011 / Accepted: 21 June 2011 / Published: 22 June 2011 Abstract: Certain triple nucleoside/tide reverse transcriptase inhibitor (NRTI) regimens containing tenofovir (TDF) have been associated with rapid early treatment failure. The mechanism is unknown, but may be at the level of drug transport. We measured the 3 lipophilicity of the drugs [ H]-lamivudine (3TC), -didanosine (ddI), -TDF and -ABC. Peripheral blood mononuclear cells (PBMCs) were used to evaluate drug–drug interactions at the level of drug transport. PBMCs were measured for the expression of P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP) by flow cytometry. The rank order o