Factors Influencing Rifampicin Autoinduction in Adult Pulmonary Tuberculosis Patients
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To demonstrate autoinduction and determine the factors associated with inter-individual variability in autoinduction of rifampicin at induction phase.
Pulmonary tuberculosis patients of either genders to be started on anti-tubercular therapy were enrolled into the study. Single blood sample at preinduction and induction phase was withdrawn by venipuncture. Serum rifampicin concentrations were estimated using LC-MS. All statistical analysis were carried out using IBM-SPSS 17.0 and graph pad prism 7.0.
Significant reduction in rifampicin Cmax was observed after 28 days (<0.0001). Though all patients displayed significant reduction in Cmax, wide inter-individual variability was observed in change in rifampicin Cmax after 28 days (ΔCmax with a mean (SD) ΔCmax of 5.448 (2.79) mcg/ml. Multivariate analysis showed hepatic function and smoking history to be explanatory variables of inter-individual differences in rifampicin autoinduction. However, unexplained variability was observed possibly due to genetic and environmental factors.
In spite of factors identified in this study, unexplained variability observed in magnitude of autoinduction could be attributed to genetic polymorphisms in regulatory proteins of enzyme induction. Hence there is crucial need for genetic association studies, as decreased exposure to rifampicin is often associated with treatment failure and emergence of drug resistance strains.
Autoinduction, Cmax, polymorphisms, pulmonary tuberculosis, rifampicin.