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Sökning: onr:"swepub:oai:DiVA.org:uu-458778" > A Population Pharma...

A Population Pharmacokinetic Modeling and Simulation Study of Posaconazole Oral Suspension in Immunocompromised Pediatric Patients : A Short Communication

Elkayal, Omar (författare)
Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.
Spriet, Isabel (författare)
Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium.
Uyttebroeck, Anne (författare)
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 (författare)
Fundeni Clin Inst, Dept Pediat, Bucharest, Romania.;Carol Davila Univ Med & Pharm, Dept Pediat, Bucharest, Romania.
Annaert, Pieter (författare)
Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.
Allegaert, Karel (författare)
Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Katholieke Univ Leuven, Woman & Child Unit, Dept Dev & Regenerat, Leuven, Belgium.
Smits, Anne (författare)
Katholieke Univ Leuven, Woman & Child Unit, Dept Dev & Regenerat, Leuven, Belgium.;Univ Hosp Leuven, Neonatal Intens Care Unit, Leuven, Belgium.
Van Daele, Ruth (författare)
Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium.
Dreesen, Erwin (författare)
Uppsala universitet,Institutionen för farmaci,Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium
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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)
LIPPINCOTT WILLIAMS & WILKINS, 2021
2021
Engelska.
Ingår i: Therapeutic Drug Monitoring. - : LIPPINCOTT WILLIAMS & WILKINS. - 0163-4356 .- 1536-3694. ; 43:4, s. 512-518
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

posaconazole
pediatrics
therapeutic drug monitoring
population pharmacokinetics
oral suspension
Pharmacology
Farmakologi

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