Pharmaceutics 2011, 3(2), 326-337; doi:10.3390/pharmaceutics3020326
Article

Interactions of Tenofovir, Lamivudine, Abacavir and Didanosine in Primary Human Cells

1,2,* email and 2
Received: 26 May 2011; in revised form: 8 June 2011 / Accepted: 21 June 2011 / Published: 22 June 2011
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 lipophilicity of the drugs [3H]-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 of the lipophilicity of the drugs were ABC>>>3TC³ddI>TDF. The accumulation of [3H]-3TC, -ddI and -TDF were temperature sensitive (suggesting facilitated transport), in contrast to [3H]-ABC. ABC reduced the accumulation of [3H]-3TC, and cell fractionation experiments suggested this was mainly in membrane-bound [3H]-3TC. ABC/TDF and ABC/ddI increased the accumulation of [3H]-3TC and 3TC/TDF also increased the accumulation of [3H]-TDF. In contrast, none of the NRTI/NtRTI incubations (alone or in combination) altered the accumulation of [3H]-ABC and -ddI. PBMC expression of P-gp, MRP1 and BCRP were detected, but none correlated with the accumulation of the drugs. The high failure rates seen with TDF, ABC and 3TC are not fully explained by an interaction at transporter level.
Keywords: tenofovir; lamivudine; abacavir; didanosine; drug transport
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MDPI and ACS Style

Janneh, O.; Khoo, S.H. Interactions of Tenofovir, Lamivudine, Abacavir and Didanosine in Primary Human Cells. Pharmaceutics 2011, 3, 326-337.

AMA Style

Janneh O, Khoo SH. Interactions of Tenofovir, Lamivudine, Abacavir and Didanosine in Primary Human Cells. Pharmaceutics. 2011; 3(2):326-337.

Chicago/Turabian Style

Janneh, Omar; Khoo, Saye H. 2011. "Interactions of Tenofovir, Lamivudine, Abacavir and Didanosine in Primary Human Cells." Pharmaceutics 3, no. 2: 326-337.

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