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The Potential for T...
The Potential for Treatment Shortening With Higher Rifampicin Doses : Relating Drug Exposure to Treatment Response in Patients With Pulmonary Tuberculosis
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- Svensson, Elin M., 1985- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands
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- Svensson, Robin J. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- te Brake, Lindsey H. M. (författare)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands
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- Boeree, Martin J. (författare)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Lung Dis, Med Ctr, Nijmegen, Netherlands
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- Heinrich, Norbert (författare)
- Univ Munich LMU, Med Ctr, Munich, Germany;German Ctr Infect Res DZIF, Munich Partner Site, Munich, Germany
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- Konsten, Sarah (författare)
- Univ Munich LMU, Med Ctr, Munich, Germany;German Ctr Infect Res DZIF, Munich Partner Site, Munich, Germany
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- Churchyard, Gavin (författare)
- South African Med Res Council, Advancing Treatment & Care TB&HIV, Johannesburg, South Africa;Aurum Inst, Johannesburg, South Africa;Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa
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- Dawson, Rodney (författare)
- Univ Cape Town, Lung Inst, Cape Town, South Africa
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- Diacon, Andreas H. (författare)
- Univ Stellenbosch, Cape Town, South Africa
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- Kibiki, Gibson S. (författare)
- Kilimanjaro Clin Res Inst, Moshi, Tanzania
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- Minja, Lilian T. (författare)
- Ifakara Hlth Inst, Bagamoyo, Tanzania
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- Ntingiya, Nyanda E. (författare)
- NIMR Mbeya Med Res Ctr, Mbeya, Tanzania
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- Saone, Ian (författare)
- Univ Witwatersrand, Johannesburg, South Africa
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- Gillespie, Stephen H. (författare)
- Univ St Andrews, St Andrews, Fife, Scotland
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- Hoelscher, Michael (författare)
- Univ Munich LMU, Med Ctr, Munich, Germany;German Ctr Infect Res DZIF, Munich Partner Site, Munich, Germany
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- Phillips, Patrick P. J. (författare)
- UCL, MRC Clin Trials Unit, London, England;Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA
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- Simonsson, Ulrika S H, Professor (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Aarnoutse, Rob (författare)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands
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(creator_code:org_t)
- 2018-03-21
- 2018
- Engelska.
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Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 67:1, s. 34-41
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background. Tuberculosis remains a huge public health problem and the prolonged treatment duration obstructs effective tuberculosis control. Higher rifampicin doses have been associated with better bactericidal activity, but optimal dosing is uncertain. This analysis aimed to characterize the relationship between rifampicin plasma exposure and treatment response over 6 months in a recent study investigating the potential for treatment shortening with high-dose rifampicin. Methods. Data were analyzed from 336 patients with pulmonary tuberculosis (97 with pharmacokinetic data) treated with rifampicin doses of 10, 20, or 35 mg/kg. The response measure was time to stable sputum culture conversion (TSCC). We derived individual exposure metrics with a previously developed population pharmacokinetic model of rifampicin. TSCC was modeled using a parametric time-to-event approach, and a sequential exposure-response analysis was performed. Results. Higher rifampicin exposures increased the probability of early culture conversion. No maximal limit of the effect was detected within the observed range. The expected proportion of patients with stable culture conversion on liquid medium at week 8 was predicted to increase from 39% (95% confidence interval, 37%-41%) to 55% (49%-61%), with the rifampicin area under the curve increasing from 20 to 175 mg/L.h (representative for 10 and 35 mg/kg, respectively). Other predictors of TSCC were baseline bacterial load, proportion of culture results unavailable, and substitution of ethambutol for either moxifloxacin or SQ109. Conclusions. Increasing rifampicin exposure shortened TSCC, and the effect did not plateau, indicating that doses >35 mg/kg could be yet more effective. Optimizing rifampicin dosage while preventing toxicity is a clinical priority.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- high-dose rifampicin
- pharmacometrics
- PK-PD
- exposure-response
- sputum culture conversion
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Svensson, Elin M ...
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Svensson, Robin ...
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te Brake, Lindse ...
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Boeree, Martin J ...
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Heinrich, Norber ...
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Konsten, Sarah
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Churchyard, Gavi ...
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Dawson, Rodney
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Diacon, Andreas ...
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Kibiki, Gibson S ...
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Minja, Lilian T.
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Ntingiya, Nyanda ...
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Saone, Ian
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Gillespie, Steph ...
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Hoelscher, Micha ...
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Phillips, Patric ...
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Simonsson, Ulrik ...
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Aarnoutse, Rob
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