Darunavir/ritonavir and efavirenz exert differential effects on MRP1 transporter expression and function in healthy volunteers

Lawrence S. Lee, Gaik H. Soon, Ping Shen, Eu Leong Yong, Charles Flexner, Paul Pham

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: The efflux transporter MRP1 actively transports antiretroviral and reduces intracellular accumulation In peripheral blood mononuclear cells (PBMCs). We studled MRP1 expression and function In healthy volunteers treated with darunavir/ritonavir and efavirenz. Methods: Seven healthy HIV-negative volunteers were recruited. PBMCs were collected at baseline, 9 days after administration of darunavir (900 mg) and ritonavir (100 mg) once daily, 9 days after coadministration of darunavir/ritonavir and efavirenz (600 mg) once daily and 13 days after administration of efavirenz alone. MRP1 expression was measured in PBMCs using flow cytometry with fluorescein isothiocyanate- conjugated antibody against MRP1 m6. MRP1 expression was also measured in CD4+ T-cells with a phycoerythrin-conjugated antibody against CD4. MRP1 efflux function was assessed by incubating PBMCs with carboxyfluorescein diacetate (CFDA) and comparing CFDA fluorescence with and without the modulators MK571 and probenecid. Results: MRP1 expression was reduced after darunavir/ ritonavir administration (geometric mean ratio [GMR] 0.58, 95% confidence interval [95% Cl] 0.51-0.65; P<0.001) and darunavir/ritonavir plus efavirenz coadministration (GMR 0.74, 95% Cl 0.64-0.84; P=0.001), but not after efavirenz administration alone (GMR 0.82, 95% Cl 0.64-1.06; P=0.10). MRP1 protein expression was 41% higher in CD4+ T-cells. MRP1 efflux function was increased after efavirenz administration (GMR 3.13, 95% Cl 2.73-3.59; P<0.001) and darunavir/ritonavir plus efavirenz coadministration (GMR 4.35, 95% Cl 3.35-5.68; P<0.001), but not after darunavir/ritonavir administration (GMR 1.06,§ 95% Cl 0.80-1.42; P=0.42). Conclusions: Darunavir/ritonavir and efavirenz treatment exerted differential effects on MRP1 expression and function. These effects could potentially alter antiviral activity, especially in CD4+ T-cells.

Original languageEnglish (US)
Pages (from-to)275-279
Number of pages5
JournalAntiviral therapy
Issue number2
StatePublished - 2010

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases


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