Effects of type 2 diabetes mellitus on the population pharmacokinetics of rifampin in tuberculosis patients

The effect of diabetes control status on treatment response in pulmonary tuberculosis: a prospective study

“…One study reported that plasma concentrations of isoniazid and rifampicin are decreased in diabetic populations compared with non-diabetic populations 27. Another study showed that the volume of distribution and the absorption rate constant of rifampicin were affected by DM 28. In addition, one study suggested that plasma glucose concentration was associated with rifampicin concentration 29…”

Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring

“…It should be noted that in some studies, only the 2-and 6-h plasma concentrations of the anti-TB drugs were measured, whereas for other studies, the intensive blood sampling or the population pharmacokinetic approach was used. In addition, it seems that the higher body weight of DM patients in some of these studies may explain the observed lower-plasma concentrations of rifampicin [67,70]. Consequently, it is not certain that the well-documented poor anti-TB treatment outcome in patients with DM is due to altered pharmacokinetics leading to low anti-TB drug plasma concentrations.…”

“…Several studies have investigated the effect of DM on the plasma concentrations of first-line anti-TB drugs [61,[66][67][68][69][70]. The results, however, are conflicting; in some studies, DM was associated with decreased plasma levels of rifampicin and isoniazid [66,69,70], whereas in others, there was no clear relationship between the plasma concentrations of first-line anti-TB drugs and DM [61,67,68]. It should be noted that in some studies, only the 2-and 6-h plasma concentrations of the anti-TB drugs were measured, whereas for other studies, the intensive blood sampling or the population pharmacokinetic approach was used.…”

Fixed-dose combination associated with faster time to smear conversion compared to separate tablets of anti-tuberculosis drugs in patients with poorly controlled diabetes and pulmonary tuberculosis in Qatar

“…Mechanistically, metformin has shown ability to selectively induce mycobacterial mitochondrial reactive oxygen species production, and facilitate phagosome-lysosome fusion [ 17 ]. Furthermore, due to altered pharmacokinetics, delayed gastric emptying, and the difference in pill burden, diabetic patients may have different response to FDC and ST regimens compared to other populations [ 12 – 14 , 18 ]. Given these direct anti-mycobacterial effects of metformin and that previous studies of FDC and ST have demonstrated similar efficacy in patients with TB [ 19 – 26 ], but diabetic patients were either excluded or did not have their outcomes specifically stated, it is increasingly relevant to understand if FDC or ST regimens perform differently in patients with diabetes and how metformin may alter these regimen differences.…”