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A Population Pharma...
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Elkayal, OmarKatholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.
(författare)
A Population Pharmacokinetic Modeling and Simulation Study of Posaconazole Oral Suspension in Immunocompromised Pediatric Patients : A Short Communication
- Artikel/kapitelEngelska2021
Förlag, utgivningsår, omfång ...
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Wolters Kluwer,2021
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printrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-458778
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-458778URI
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https://doi.org/10.1097/FTD.0000000000000877DOI
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Språk:engelska
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Sammanfattning på:engelska
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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.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Spriet, IsabelKatholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium.
(författare)
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Uyttebroeck, AnneKatholieke Univ Leuven, Paediat Oncol Unit, Dept Oncol, Leuven, Belgium.;Univ Hosp Leuven, Pediat Oncol & Hematol Dept, Leuven, Belgium.
(författare)
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Colita, AncaFundeni Clin Inst, Dept Pediat, Bucharest, Romania.;Carol Davila Univ Med & Pharm, Dept Pediat, Bucharest, Romania.
(författare)
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Annaert, PieterKatholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.
(författare)
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Allegaert, KarelKatholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Katholieke Univ Leuven, Woman & Child Unit, Dept Dev & Regenerat, Leuven, Belgium.
(författare)
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Smits, AnneKatholieke Univ Leuven, Woman & Child Unit, Dept Dev & Regenerat, Leuven, Belgium.;Univ Hosp Leuven, Neonatal Intens Care Unit, Leuven, Belgium.
(författare)
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Van Daele, RuthKatholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Pharm Dept, Leuven, Belgium.
(författare)
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Dreesen, ErwinUppsala universitet,Institutionen för farmaci(Swepub:uu)erwdr842
(författare)
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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)
Sammanhörande titlar
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Ingår i:Therapeutic Drug Monitoring: Wolters Kluwer43:4, s. 512-5180163-43561536-3694
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