Population Pharmacokinetic Model Development and Simulation for Recombinant Erwinia Asparaginase Produced in Pseudomonas fluorescens (JZP-458).

JZP-458 is a recombinant Erwinia asparaginase produced using a novel Pseudomonas fluorescens expression platform that yields an enzyme expected to lack immunologic cross-reactivity to Escherichia coli-derived asparaginases. It is being developed as part of a multiagent chemotherapeutic regimen to treat acute lymphoblastic leukemia or lymphoblastic lymphoma patients who develop E coli-derived asparaginase hypersensitivity. A population pharmacokinetic (PopPK) model was developed for JZP-458 using serum asparaginase activity (SAA) data from a phase 1, single-dose study (JZP458-101) in healthy adults.

Antiretroviral Drug Concentrations in Breastmilk, Maternal HIV Viral Load, and HIV Transmission to the Infant: Results From the BAN Study.

Background: Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission.

Methods: In this cohort study with 2-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals, and Nutrition study. Among these, we included all mothers who transmitted HIV to their infants between 2 and 28 weeks and 15% of mothers who did not (n = 27 and 227, respectively).

Pharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy Volunteers.

Background: CW002 is an investigational nondepolarizing, neuromuscular blocking agent with a rapid onset and intermediate duration of action in animals. This is a single ascending dose, healthy subject study exploring tolerability, pharmacokinetics, and potency.

Methods: Population pharmacokinetic and pharmacokinetic/pharmacodynamic models were developed using plasma drug concentration data from a previously published dose-response study in 28 healthy subjects receiving single doses of CW002 during sevoflurane anesthesia.

Transporter-Mediated Alterations in Patients With NASH Increase Systemic and Hepatic Exposure to an OATP and MRP2 Substrate.

The expression of hepatic transporters, including organic anion transporting polypeptides (OATPs) and multidrug resistance-associated proteins (MRPs), is altered in nonalcoholic steatohepatitis (NASH); however, functional data in humans are lacking. In this study, Tc-mebrofenin (MEB) was used to evaluate OATP1B1/1B3 and MRP2 function in NASH patients. Healthy subjects (n = 14) and NASH patients (n = 7) were administered MEB (∼2.