Chemical and Pharmacologic Phenomena | Open Access Articles

Population Pharmacokinetics And Dosing Simulations Of Pentobarbital In The Pediatric Population, Victoria Etges Helfer, Lorena Medina-Aymerich, William J. Muller, Marisa Meyer, Amira Al-Uzri, Russell Mcculloh, Chi D. Hornik, Stephen J. Balevic, Rachel G. Greenberg, Daniel K. Benjamin, Sarah G. Anderson, Daniel Gonzalez

Department of Pediatrics Faculty Papers

Pentobarbital is a barbiturate with sedative and anticonvulsant properties, occasionally used in pediatric patients for preoperative sedation, deep sedation during mechanical ventilation, and seizure control. Despite its long-standing clinical use, age-appropriate dosing remains challenging due to variability across studies and limited pediatric pharmacokinetic (PK) data. This study (NCT01431326) aimed to characterize the population pharmacokinetics of pentobarbital in pediatric patients (birth to 21 years) and evaluate dosing strategies using model-based simulations. A two-compartment population PK model, allometrically scaled to total body weight, adequately described pentobarbital plasma concentrations, with no additional covariates identified as significant. Simulations were conducted across four age groups: …

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Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

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Age-Dependent Absolute Abundance Of Hepatic Carboxylesterases (Ces1 And Ces2) By Lc-Ms/Ms Proteomics: Application To Pbpk Modeling Of Oseltamivir In Vivo Pharmacokinetics In Infants., Mikael Boberg, Marc Vrana, Aanchal Mehrotra, Robin E. Pearce, Andrea Gaedigk, Deepak Kumar Bhatt, J Steven Leeder, Bhagwat Prasad

Manuscripts, Articles, Book Chapters and Other Papers

The age-dependent absolute protein abundance of carboxylesterase (CES) 1 and CES2 in human liver was investigated and applied to predict infant pharmacokinetics (PK) of oseltamivir. The CES absolute protein abundance was determined by liquid chromatography-tandem mass spectrometry proteomics in human liver microsomal and cytosolic fractions prepared from tissue samples obtained from 136 pediatric donors and 35 adult donors. Two surrogate peptides per protein were selected for the quantification of CES1 and CES2 protein abundance. Purified CES1 and CES2 protein standards were used as calibrators, and the heavy labeled peptides were used as the internal standards. In hepatic microsomes, CES1 and …

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Department of Pediatrics Faculty Papers

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Manuscripts, Articles, Book Chapters and Other Papers