Prevalence of p-glycoprotein (PGP) expression, function and its effect on efficacy of rifampicin in patients with lymph node tuberculosis

Objective: P-glycoprotein (PGP) overexpression may be one of the operating mechanisms of suboptimal responses to antitubercular treatment (ATT) in patients with lymph node tuberculosis. This might become responsible for the development of drug resistance later due to exposure of subtherapeutic concentrations to the mycobacteria. In this study we aim to study the prevalence of PGP expression and function and its relationship with serum concentrations of Rifampicin in consecutive patients with lymph node tuberculosis.

Methods: All newly diagnosed treatment naïve subjects with a confirmed diagnosis of tubercular lymphadenopathy were included in the study and the expression and function of PGP in blood was determined by flowcytometry at baseline and after two months of treatment. Serum levels of Rifampicin was measured at 2 months by high performance liquid chromatography (HPLC). The mean net PGP expression expressed as percent and relative fluorescence indices (RFI) of PGP expression and function respectively was compared at baseline at 2 months and was also correlated with serum rifampicin levels.

Results: The mean net PGP expression, RFI of PGP expression and RFI of PGP function were significantly higher in patients with lymph node tuberculosis as compared to healthy controls and the mean net PGP expression and RFI of PGP expression were significantly higher at 2 months as compared to baseline (25.64 ± 5.18% vs. 27.68 ± 4.89%, 4.34 ± 1.09% vs. 4.95 ± 1.55). There was no significant difference in RFI of PGP expression and RFI of PGP function between the poor-responders and responders at baseline and 2 months however there was a trend towards significantly higher net PGP expression amongst poor responders at baseline. The mean serum rifampicin levels were 10.74 ± 2.36 μg/ml in the responder group and 7.86 ± 1.21 μg/ml in the non-responder group and the difference between the two was statistically significant (p = 0.004).

Conclusions: Overexpression of PGP is common in patients with lymph node tuberculosis and leads to lower concentrations of Rifampicin in blood which subsequently may give rise to development of drug resistance. This is also responsible for poor therapeutic responses in these patients. Nonspecific inhibitors of PGP may be used in conjunction with ATT to augment therapeutic response in such cases.