Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis. Schutz, C., Chirehwa, M., Barr, D., Ward, A., Janssen, S., Burton, R., Wilkinson, R. J, Shey, M., Wiesner, L., Denti, P., McIlleron, H., Maartens, G., & Meintjes, G. A British Journal of Clinical Pharmacology, 86(5):966–978, Wiley, jan, 2020. ![Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 11 downloads Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 $μ$g mL–1, P =.223; 3.6 vs 3.5 $μ$g mL–1, P =.569; 50.1 vs 46.8 $μ$g mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate \textgreater2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival.
@article{Schutz2020,
abstract = {Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19{\%}). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 $\mu$g mL–1, P =.223; 3.6 vs 3.5 $\mu$g mL–1, P =.569; 50.1 vs 46.8 $\mu$g mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61{\%} and 39{\%} of inpatients and 44{\%} and 35{\%} of outpatients. Rifampicin exposure was higher in patients with lactate {\textgreater}2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61{\%} and 39{\%} of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival.},
author = {Schutz, Charlotte and Chirehwa, Maxwell and Barr, David and Ward, Amy and Janssen, Saskia and Burton, Rosie and Wilkinson, Robert J and Shey, Muki and Wiesner, Lubbe and Denti, Paolo and McIlleron, Helen and Maartens, Gary and Meintjes, Graeme A},
doi = {10.1111/bcp.14207},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Schutz et al. - 2020 - Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberc.pdf:pdf},
issn = {13652125},
journal = {British Journal of Clinical Pharmacology},
keywords = {OA,fund{\_}ack,human immunodeficiency virus,original,pharmacokinetics,treatment,tuberculosis},
mendeley-tags = {OA,fund{\_}ack,original},
month = {jan},
number = {5},
pages = {966--978},
pmid = {31912537},
publisher = {Wiley},
title = {{Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis}},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/bcp.14207},
volume = {86},
year = {2020}
}
Downloads: 11
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Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 $μ$g mL–1, P =.223; 3.6 vs 3.5 $μ$g mL–1, P =.569; 50.1 vs 46.8 $μ$g mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate \\textgreater2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival.","author":[{"propositions":[],"lastnames":["Schutz"],"firstnames":["Charlotte"],"suffixes":[]},{"propositions":[],"lastnames":["Chirehwa"],"firstnames":["Maxwell"],"suffixes":[]},{"propositions":[],"lastnames":["Barr"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Ward"],"firstnames":["Amy"],"suffixes":[]},{"propositions":[],"lastnames":["Janssen"],"firstnames":["Saskia"],"suffixes":[]},{"propositions":[],"lastnames":["Burton"],"firstnames":["Rosie"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Shey"],"firstnames":["Muki"],"suffixes":[]},{"propositions":[],"lastnames":["Wiesner"],"firstnames":["Lubbe"],"suffixes":[]},{"propositions":[],"lastnames":["Denti"],"firstnames":["Paolo"],"suffixes":[]},{"propositions":[],"lastnames":["McIlleron"],"firstnames":["Helen"],"suffixes":[]},{"propositions":[],"lastnames":["Maartens"],"firstnames":["Gary"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme","A"],"suffixes":[]}],"doi":"10.1111/bcp.14207","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Schutz et al. - 2020 - Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberc.pdf:pdf","issn":"13652125","journal":"British Journal of Clinical Pharmacology","keywords":"OA,fund_ack,human immunodeficiency virus,original,pharmacokinetics,treatment,tuberculosis","mendeley-tags":"OA,fund_ack,original","month":"jan","number":"5","pages":"966–978","pmid":"31912537","publisher":"Wiley","title":"Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis","url":"https://onlinelibrary.wiley.com/doi/abs/10.1111/bcp.14207","volume":"86","year":"2020","bibtex":"@article{Schutz2020,\r\nabstract = {Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19{\\%}). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 $\\mu$g mL–1, P =.223; 3.6 vs 3.5 $\\mu$g mL–1, P =.569; 50.1 vs 46.8 $\\mu$g mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61{\\%} and 39{\\%} of inpatients and 44{\\%} and 35{\\%} of outpatients. Rifampicin exposure was higher in patients with lactate {\\textgreater}2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61{\\%} and 39{\\%} of inpatients and rifampicin exposure was higher in patients with high lactate. 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