Population pharmacokinetic analysis of acetaminophen overdose with immediate release, extended release and modified release formulations
العنوان: | Population pharmacokinetic analysis of acetaminophen overdose with immediate release, extended release and modified release formulations |
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المؤلفون: | Daniel A, Spyker, Richard C, Dart, Luke, Yip, Kate, Reynolds, Scott, Brittain, Mark, Yarema |
المصدر: | Clinical Toxicology. 60:1113-1121 |
بيانات النشر: | Informa UK Limited, 2022. |
سنة النشر: | 2022 |
مصطلحات موضوعية: | Analgesics, Opioid, Cross-Over Studies, Delayed-Action Preparations, Humans, General Medicine, Drug Overdose, Toxicology, Acetaminophen |
الوصف: | The introduction of delayed release formulations of acetaminophen (APAP) has created concern about the role of formulation in overdose. We examined the APAP overdose pharmacokinetic (PK) profiles to assess the role of dose, coingestants and formulation: immediate release (IR), extended release (ER), and modified release (MR) on APAP pharmacokinetic measures.We collected by-subject APAP PK data: subject description, timed blood APAP concentrations, dose, and coingestants. We sought both overdose and randomized controlled trials (RCTs) for supratherapeutic doses involving ER or MR formulations. Data analysis and simulation used the non-linear mixed-effects modeling program NONMEM-version 7.4.The final dataset comprised 3,033 [APAP] from 356 subjects and 15 sources including 3 RCTs (179 subjects receiving IR, 122 ER, 65 MR). The final population PK (PopPK) model was a linear 2-compartment model with first-order (oral) absorption. Covariate relationships included: APAP absorption rate and bioavailability decreased with increased oral dose (Acetaminophen ER and MR formulations have slower absorption and decreased bioavailability leading to a lower |
تدمد: | 1556-9519 1556-3650 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59a4d73d544e1d80e524cf75a54d930e https://doi.org/10.1080/15563650.2022.2114361 |
رقم الأكسشن: | edsair.doi.dedup.....59a4d73d544e1d80e524cf75a54d930e |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15569519 15563650 |
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