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A Population Pharma...
A Population Pharmacokinetic Modeling and Simulation Study of Posaconazole Oral Suspension in Immunocompromised Pediatric Patients : A Short Communication
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- Elkayal, Omar (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.
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- Spriet, Isabel (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium.
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- Uyttebroeck, Anne (author)
- Katholieke Univ Leuven, Paediat Oncol Unit, Dept Oncol, Leuven, Belgium.;Univ Hosp Leuven, Pediat Oncol & Hematol Dept, Leuven, Belgium.
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- Colita, Anca (author)
- Fundeni Clin Inst, Dept Pediat, Bucharest, Romania.;Carol Davila Univ Med & Pharm, Dept Pediat, Bucharest, Romania.
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- Annaert, Pieter (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.
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- Allegaert, Karel (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Katholieke Univ Leuven, Woman & Child Unit, Dept Dev & Regenerat, Leuven, Belgium.
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- Smits, Anne (author)
- Katholieke Univ Leuven, Woman & Child Unit, Dept Dev & Regenerat, Leuven, Belgium.;Univ Hosp Leuven, Neonatal Intens Care Unit, Leuven, Belgium.
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- Van Daele, Ruth (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium.
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- Dreesen, Erwin (author)
- Uppsala universitet,Institutionen för farmaci
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Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium. (creator_code:org_t)
- Wolters Kluwer, 2021
- 2021
- English.
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In: Therapeutic Drug Monitoring. - : Wolters Kluwer. - 0163-4356 .- 1536-3694. ; 43:4, s. 512-518
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Background: Posaconazole oral suspension emerged as a promising candidate for prophylaxis of invasive fungal infections in immunocompromised children. Its pharmacodynamic advantages include a broad-spectrum activity and a favorable safety profile; however, they are overshadowed by its large pharmacokinetic (PK) variability, which might cause subtherapeutic exposure. The aim of this study was to develop a population (pop) PK model based on rich sampling data to better understand the PK of posaconazole oral suspension in pediatric patients. Methods: Data were obtained from a prospective interventional study involving hospitalized pediatric patients with a hematologic malignancy and prophylactically treated with posaconazole oral suspension. After constructing the popPK model, the probability of target attainment (PTA; 100% T >= 0.7 mg/L) for prophylaxis under fixed, body weight-based, and body surface area-based dosing was evaluated using Monte Carlo simulation. Results: Fourteen patients contributed 112 posaconazole plasma concentrations. The PK of posaconazole was adequately described by a 1-compartment model with lag time 2.71 hours [13%]; nonlinear bioavailability ED50 99.1 mg/m(2) (fixed); first-order absorption rate constant 0.325 hour(-1) [27%]; apparent volume of distribution 1150 L [34%]; and apparent clearance 15.4 L/h [24%] (similar to 70-kg individual). The bioavailability decreased in the presence of diarrhea and co-treatment with a proton pump inhibitor (PPI). The unexplained interindividual variability in posaconazole PK remained large. The PTA was <85%, irrespective of the simulated dosing strategy. Patients without diarrhea and not administered a PPI had the highest PTA (85% under the fixed 300-mg dosing 4 times per day). Conclusions: Therapeutic drug monitoring is recommended during prophylactic posaconazole therapy in immunocompromised pediatric patients. Large-scale comparative studies are needed to characterize the PK variability between different posaconazole formulations in this cohort.
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)
Keyword
- posaconazole
- pediatrics
- therapeutic drug monitoring
- population pharmacokinetics
- oral suspension
- Pharmacology
- Farmakologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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