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Prediction of Moxif...
Prediction of Moxifloxacin Concentrations in Tuberculosis Patient Populations by Physiologically Based Pharmacokinetic Modeling
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- Litjens, Carlijn H. C. (author)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands.
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- Verscheijden, Laurens F. M. (author)
- Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands.
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- Bolwerk, Celine (author)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.
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- Greupink, Rick (author)
- Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands.
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- Koenderink, Jan B. (author)
- Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands.
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- van den Broek, Petra H. H. (author)
- Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands.
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- van den Heuvel, Jeroen J. M. W. (author)
- Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands.
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- Svensson, Elin, 1985- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.
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- Boeree, Martin J. (author)
- Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pulm Dis, Med Ctr, Nijmegen, Netherlands.
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- Magis-Escurra, Cecile (author)
- Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pulm Dis, Med Ctr, Nijmegen, Netherlands.
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- Hoefsloot, Wouter (author)
- Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pulm Dis, Med Ctr, Nijmegen, Netherlands.
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- van Crevel, Reinout (author)
- Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Internal Med, Med Ctr, Nijmegen, Netherlands.
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- van Laarhoven, Arjan (author)
- Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Internal Med, Med Ctr, Nijmegen, Netherlands.
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- van Ingen, Jakko (author)
- Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands.
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- Kuipers, Saskia (author)
- Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands.
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- Ruslami, Rovina (author)
- Univ Padjadjaran, Fac Med, TB HIV Res Ctr, Bandung, Indonesia.;Univ Padjadjaran, Fac Med, Dept Biomed Sci, Div Pharmacol & Therapy, Bandung, Indonesia.
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- Burger, David M. (author)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.
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- Russel, Frans G. M. (author)
- Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands.
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- Aarnoutse, Rob E. (author)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.
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- Te Brake, Lindsey H. M. (author)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.
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Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands;Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands. Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands. (creator_code:org_t)
- 2021-10-25
- 2022
- English.
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In: Journal of clinical pharmacology. - : John Wiley & Sons. - 0091-2700 .- 1552-4604. ; 62:3, s. 385-396
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Abstract
Subject headings
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- Moxifloxacin has an important role in the treatment of tuberculosis (TB). Unfortunately, coadministration with the cornerstone TB drug rifampicin results in suboptimal plasma exposure. We aimed to gain insight into the moxifloxacin pharmacokinetics and the interaction with rifampicin. Moreover, we provided a mechanistic framework to understand moxifloxacin pharmacokinetics. We developed a physiologically based pharmacokinetic model in Simcyp version 19, with available and newly generated in vitro and in vivo data, to estimate pharmacokinetic parameters of moxifloxacin alone and when administered with rifampicin. By combining these strategies, we illustrate that the role of P-glycoprotein in moxifloxacin transport is limited and implicate MRP2 as transporter of moxifloxacin-glucuronide followed by rapid hydrolysis in the gut. Simulations of multiple dose area under the plasma concentration-time curve (AUC) of moxifloxacin (400 mg once daily) with and without rifampicin (600 mg once daily) were in accordance with clinically observed data (predicted/observed [P/O] ratio of 0.87 and 0.80, respectively). Importantly, increasing the moxifloxacin dose to 600 mg restored the plasma exposure both in actual patients with TB as well as in our simulations. Furthermore, we extrapolated the single dose model to pediatric populations (P/O AUC ratios, 1.04-1.52) and the multiple dose model to children with TB (P/O AUC ratio, 1.51). In conclusion, our combined approach resulted in new insights into moxifloxacin pharmacokinetics and accurate simulations of moxifloxacin exposure with and without rifampicin. Finally, various knowledge gaps were identified, which may be considered as avenues for further physiologically based pharmacokinetic refinement.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- drug-drug interactions
- modeling
- moxifloxacin
- physiologically based pharmacokinetics
- tuberculosis
Publication and Content Type
- ref (subject category)
- art (subject category)
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Litjens, Carlijn ...
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Verscheijden, La ...
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Bolwerk, Celine
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Greupink, Rick
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Koenderink, Jan ...
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van den Broek, P ...
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van den Heuvel, ...
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Svensson, Elin, ...
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Boeree, Martin J ...
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Magis-Escurra, C ...
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Hoefsloot, Woute ...
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van Crevel, Rein ...
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van Laarhoven, A ...
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van Ingen, Jakko
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Kuipers, Saskia
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Ruslami, Rovina
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Burger, David M.
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Russel, Frans G. ...
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Aarnoutse, Rob E ...
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Te Brake, Lindse ...
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MEDICAL AND HEAL ...
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Uppsala University