Population pharmacokinetic and pharmacokinetic-pharmacodynamic modeling of bempedoic acid and low-density lipoprotein cholesterol in healthy subjects and patients with dyslipidemia.

Population pharmacokinetics (popPK) of bempedoic acid and the popPK/pharmacodynamic (popPK/PD) relationship between bempedoic acid concentrations and serum low-density lipoprotein cholesterol (LDL-C) from baseline were characterized. A two-compartment disposition model with a transit absorption compartment and linear elimination best described bempedoic acid oral pharmacokinetics (PK). Multiple covariates, including renal function, sex, and weight, had statistically significant effects on the predicted steady-state area under the curve.

Development of a Population Pharmacokinetic Model for the Diroximel Fumarate Metabolites Monomethyl Fumarate and 2-Hydroxyethyl Succinimide Following Oral Administration of Diroximel Fumarate in Healthy Participants and Patients with Multiple Sclerosis.

Introduction: Diroximel fumarate (DRF) is a next-generation oral fumarate that is indicated in the USA for relapsing forms of multiple sclerosis (MS). A joint population pharmacokinetic model was developed for the major active metabolite (monomethyl fumarate, MMF) and the major inactive metabolite (2-hydroxyethyl succinimide, HES) of DRF.

Methods: MMF and HES data were included from 341 healthy volunteers and 48 patients with MS across 11 phase I and III studies in which DRF was administered as single or multiple doses.

Population Pharmacokinetics of Vixotrigine in Healthy Volunteers and Subjects with Trigeminal Neuralgia, Painful Lumbosacral Radiculopathy and Erythromelalgia.

Background: Vixotrigine is a voltage and use dependent sodium channel blocker currently under development for treatment of various neuropathic pain indications.

Objective: The objective of this work was to develop a population pharmacokinetic model and assess effects of various covariates on pharmacokinetic parameters of vixotrigine.

Method: Plasma concentration-time data from 12 Phase 1 or 2 studies were included in the analyses.

Population Pharmacokinetics of Pregabalin Extended-Release in Healthy Volunteers and Patients With Postherpetic Neuralgia, Fibromyalgia, and Partial-Onset Seizures.

A population pharmacokinetic (PK) model was developed to characterize the properties of pregabalin extended-release (ER) in healthy volunteers and was subsequently applied to patient data from efficacy/safety studies investigating pregabalin ER for postherpetic neuralgia, fibromyalgia, and partial-onset seizures. The impact of demographic and other covariates on PK was assessed, and various dosing scenarios were simulated to inform pregabalin ER dosing/administration instructions. Phase 1 and 3 models were developed using data from 14 phase 1 studies (12 627 samples from 335 participants receiving pregabalin immediate-release [IR] or ER) and 3 phase 3 studies (2591 samples from 1235 patients receiving pregabalin ER), respectively.

Effect of the gastrointestinal prokinetic agent erythromycin on the pharmacokinetics of pregabalin controlled-release in healthy individuals: a phase I, randomized crossover trial.

Background And Objectives: The controlled-release (CR) formulation of pregabalin is designed to remain in the stomach for a prolonged period while slowly releasing pregabalin for absorption in the small intestine. This study evaluated the effect of the gastrointestinal prokinetic agent, erythromycin, on the pharmacokinetics of a single dose of pregabalin CR 330 mg administered following an evening meal and the safety and tolerability of a single dose of pregabalin CR 330 mg when administered with and without multiple doses of erythromycin 500 mg.

Methods: This was a phase I, open-label, randomized, two-period, two-treatment crossover study.