Dried Blood Spot Sampling to Assess Rifampicin Exposure and Treatment Outcomes among Native and Non-Native Tuberculosis Patients in Paraguay: An Exploratory Study
The aim of this study was to evaluate the difference in drug exposure of rifampicin in native versus non-native Paraguayan populations using dried blood spots (DBS) samples collected utilizing a limited sampling strategy. This was a prospective pharmacokinetic study that enrolled hospitalized tuberc...
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| Main Authors: | , , , , , , , , |
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| Format: | Book |
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MDPI AG,
2023-03-01T00:00:00Z.
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| Summary: | The aim of this study was to evaluate the difference in drug exposure of rifampicin in native versus non-native Paraguayan populations using dried blood spots (DBS) samples collected utilizing a limited sampling strategy. This was a prospective pharmacokinetic study that enrolled hospitalized tuberculosis (TB) patients from both native and non-native populations receiving oral rifampicin 10 mg/kg once-daily dosing. Steady-state DBS samples were collected at 2, 4, and 6 h after intake of rifampicin. The area under the time concentration curve 0-24 h (AUC<sub>0-24</sub>) was calculated using a Bayesian population PK model. Rifampicin AUC<sub>0-24</sub> < 38.7 mg*h/L was considered as low. The probability of target attainment (PTA) was calculated using AUC<sub>0-24</sub>/MIC > 271 as a target and estimated MIC values of 0.125 and 0.25 mg/L. In total, 50 patients were included. Native patients (<i>n</i> = 30) showed comparable drug exposure to the non-natives (<i>n</i> = 20), median AUC<sub>0-24</sub> 24.7 (17.1-29.5 IQR) and 21.6 (15.0-35.4 IQR) mg*h/L (<i>p</i> = 0.66), respectively. Among total patients, only 16% (<i>n</i> = 8) had a rifampicin AUC<sub>0-24</sub> > 38.7 mg*h/L. Furthermore, PTA analysis showed that only 12 (24%) of the patients met a target AUC<sub>0-24</sub> /MIC ≥ 271, assuming an MIC of 0.125 mg/L, which plummeted to 0% at a wild-type MIC of 0.25 mg/L. We successfully used DBS and limited sampling for the AUC<sub>0-24</sub> estimation of rifampicin. Currently, our group, the EUSAT-RCS consortium, is preparing a prospective multinational, multicenter phase IIb clinical trial evaluating the safety and efficacy of high-dose rifampicin (35 mg/kg) in adult subjects using the DBS technique for AUC<sub>0-24</sub> estimation. |
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| Item Description: | 10.3390/pharmaceutics15041089 1999-4923 |