The recent pharmacogenetic study in HIV patients www.selleckchem.com/products/MLN-2238.html co admi nistrated with efavirenz and rifampicin demonstrated that patients carrying TT genotype had significantly higher mean plasma efavirenz but lower oral clearance, indicating that rifampicin does not fully reverse the poor metabolizer phenotype and that TT genotype can be used to identify poor metabolizers of efavirenz even in patients co administrated with rifampicin. Consis tently, the present results also indicated that rifampicin coadministration in HIVTB infected patients did not significantly alter plasma efavirenz and nevirapine levels in patients with TT genotype. Other possible factors that might affect the plasma drug levels could be excluded Inhibitors,Modulators,Libraries since they were carefully controlled.
Although rifampicin can cause the decrease in NNRTI concentrations, the mean plasma efavirenz and nevira pine concentrations in all studied patients with TT, GT and GG genotypes had Inhibitors,Modulators,Libraries plasma drug levels above the minimum recommendation. One important conclusion from our recent prospective and randomized clinical trial in patients with concurrent HIVTB receiving rifampicin is that the standard dosage of efavirenz 600 mg or nevirapine 400 mg per day and co adminis tration with rifampicin was adequate for HIV 1 suppres sion, however, variation in the plasma drug levels in some patients were found, which might be due to the genetic variations among individuals. Although we reported recently that high body weights of the patients were associated with a low efavirenz C12 at weeks 6 and 12 of ART, the present results demonstrated that the body weights did not differ among patients with dif ferent genotypes of CYP2B6 G516T polymorphism.
The present results thus demonstrated that rifampicin has very small effects on efavirenz and nevirapine plasma drug. The advantage of our present study over previous studies is that plasma efavirenz and nevirapine concen trations during co administration of Inhibitors,Modulators,Libraries rifampicin could be compared with those without rifampicin after complet ing TB drug Inhibitors,Modulators,Libraries treatment. In general, the high plasma efavirenz and nevirapine levels could lead to the adverse effect such as rash, hepatitis, and neuropsychological toxicity. In order to reduce such adverse effects, Inhibitors,Modulators,Libraries several studies attempted to test the feasibility of genotype based dose reduction of efavirenz in African American and Japanese HIV infected patients and showed that efavirenz dose reduction is feasible and can reduce efa virenz associated central nervous system symptoms in homozygotes of CYP2B6 G516T.
Although patients with CYP2B6 516TT in our cohort had obviously high plasma efavirenz levels at all time points and certain degree of central nervous system and psychiatric mani festations, most they were all well tolerated with the adverse effects. The adverse drug events have not recorded in nevirapine based treatment probably due to the limited number of patients with homozygous TT.