Vogensen, V. (Vanessa) (2021) Effect of rifampicin in reducing moxifloxacin exposure in patients with isoniazid-resistant or –intolerant tuberculosis and the implications of a higher moxifloxacin dose. thesis, Medicine.
Full text available on request.Abstract
International treatment guidelines for rifampicin-susceptible isoniazid-resistant tuberculosis (TB) have recently changed to include levofloxacin. Moxifloxacin, another later generation fluoroquinolone, could be a good alternative but rifampicin considerably decreases moxifloxacin drug exposure. This retrospective study of routine care data from a Dutch TB center investigated both the effect of rifampicin coadministration and that of different rifampicin and moxifloxacin doses on moxifloxacin exposure in patients with isoniazid-resistant or –intolerant TB. Moxifloxacin drug exposure measured from January 2015 to September 2020 was compared between thirty-one patients with isoniazid-resistant or –intolerant tuberculosis who received rifampicin, and twenty patients with tuberculosis who did not. Moxifloxacin exposure among different rifampicin or moxifloxacin doses was also studied. The ratio of geometric means (RGM) of the moxifloxacin area under the curve (AUC(0–24)) when rifampicin was coadministered compared to when only moxifloxacin was administered was 0.61 (90% CI 0.53, 0.70). Peak concentration was significantly reduced (RGM 0.81 (90% CI 0.70, 0.94)) and apparent clearance significantly increased (RGM1.70 (90% CI 1.51, 1.91)). Next to a significant increase in moxifloxacin AUC(0-24) for a 600 mg/day moxifloxacin dose, 7/8 (87.5%) patients reached the pharmacokinetic/pharmacodynamic (PK/PD) target. This study showed a 39% decrease in moxifloxacin exposure when rifampicin was coadministered, a larger decrease than previously reported. A 600 mg moxifloxacin dose resulted in promising PK/PD target attainment. More extensive research is warranted to compare effectiveness and safety of higher moxifloxacin doses with the recommended levofloxacin for isoniazid-resistant and -intolerant TB.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Akkerman, dr. O. |
| Faculty: | Medical Sciences |
| Date Deposited: | 05 Jan 2022 11:05 |
| Last Modified: | 05 Jan 2022 11:05 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2943 |
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