Clinical Pharmacokinetics

http://link.springer.com/journal/40262

List of Papers (Total 163)

A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus Following Pediatric Renal Transplantation

Background Multiple clinical, demographic, and genetic factors affect the pharmacokinetics of tacrolimus in children, yet in daily practice, a uniform body-weight based starting dose is used. It can take weeks to reach the target tacrolimus pre-dose concentration. Objectives The objectives of this study were to determine the pharmacokinetics of tacrolimus immediately after kidney ...

Review of the Clinical Pharmacokinetics and Pharmacodynamics of Alemtuzumab and Its Use in Kidney Transplantation

Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as induction and anti-rejection therapy. The objective of this review ...

Explaining Ethnic Variability of Transporter Substrate Pharmacokinetics in Healthy Asian and Caucasian Subjects with Allele Frequencies of OATP1B1 and BCRP: A Mechanistic Modeling Analysis

Background Ethnic variability in the pharmacokinetics of organic anion transporting polypeptide (OATP) 1B1 substrates has been observed, but its basis is unclear. A previous study hypothesizes that, without applying an intrinsic ethnic variability in transporter activity, allele frequencies of transporters cannot explain observed ethnic variability in pharmacokinetics. However, ...

Clinical Pharmacokinetic Characteristics of Cebranopadol, a Novel First-in-Class Analgesic

Background and Objectives Cebranopadol is a novel first-in-class analgesic acting as a nociceptin/orphanin FQ peptide and opioid peptide receptor agonist with central analgesic activity. It is currently in clinical development for the treatment of chronic pain conditions. This trial focuses on the clinical pharmacokinetic (PK) properties of cebranopadol after oral single- and ...

Population Pharmacokinetic Modeling of Olaratumab, an Anti-PDGFRα Human Monoclonal Antibody, in Patients with Advanced and/or Metastatic Cancer

Background and Objectives Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with ...

A Population Pharmacokinetic and Pharmacodynamic Analysis of Abemaciclib in a Phase I Clinical Trial in Cancer Patients

Background and Objectives Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated clinical activity in a number of different cancer types. The objectives of this study were to characterize the pharmacokinetics of abemaciclib in cancer patients using population pharmacokinetic (popPK) modeling, and to evaluate target engagement at clinically relevant dose ...

A Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Vedolizumab

Vedolizumab is a humanized anti-α4β7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α4β7-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD), vedolizumab is administered as a 300 ...

An Open-Label Crossover Study of the Pharmacokinetics of the 60-mg Edoxaban Tablet Crushed and Administered Either by a Nasogastric Tube or in Apple Puree in Healthy Adults

Background Edoxaban is an orally active, direct factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation and for the treatment of venous thromboembolism. Objectives This study assessed the pharmacokinetics, safety, and tolerability of the edoxaban 60-mg tablet crushed and administered via a nasogastric tube in a water ...

Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide

Introduction Obesity is associated with many pathophysiological changes that may result in altered drug metabolism. The aim of this study is to investigate the influence of obesity on the pharmacokinetics of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a combined analysis in morbidly obese patients and non-obese healthy volunteers. Methods In ...

Phase I Clinical Study of ZYAN1, A Novel Prolyl-Hydroxylase (PHD) Inhibitor to Evaluate the Safety, Tolerability, and Pharmacokinetics Following Oral Administration in Healthy Volunteers

Objective This phase I study of ZYAN1 was conducted to evaluate the safety, tolerability, and pharmacokinetics following oral administration in healthy volunteers. Methods The study was a randomized, double-blind, placebo-controlled phase I study carried out in two parts in addition to a third part involving an open-label study to evaluate the food/sex effect. A total of 100 ...

Comparison of a Novel Formulation of Abiraterone Acetate vs. the Originator Formulation in Healthy Male Subjects: Two Randomized, Open-Label, Crossover Studies

Background and Objective Abiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer. The originator abiraterone acetate (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic variability in abiraterone exposure. Abiraterone acetate fine particle (AAFP) is a proprietary formulation (using SoluMatrix Fine Particle ...

Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment

Background The pharmacokinetics and tolerability of semaglutide, a once-weekly human glucagon-like peptide-1 analog in development for the treatment of type 2 diabetes mellitus, were investigated in subjects with/without renal impairment (RI). Methods Fifty-six subjects, categorized into renal function groups [normal, mild, moderate, severe, and end-stage renal disease (ESRD)], ...

Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects

Background and Objective Semaglutide is a glucagon-like peptide-1 analogue in development for the once-weekly treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (metformin, warfarin, atorvastatin and digoxin) was evaluated in healthy subjects. Methods Subjects received metformin (500 mg twice daily for 3.5 days), ...

Population Pharmacokinetic Analysis of Ixazomib, an Oral Proteasome Inhibitor, Including Data from the Phase III TOURMALINE-MM1 Study to Inform Labelling

Ixazomib is an oral proteasome inhibitor, approved in USA, Canada, Australia and Europe in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. We report a population pharmacokinetic model-based analysis for ixazomib that was pivotal in describing the clinical pharmacokinetics of ixazomib, ...

Time-to-Seizure Modeling of Lacosamide Used in Monotherapy in Patients with Newly Diagnosed Epilepsy

Objectives To quantify the relationship between exposure to lacosamide monotherapy and seizure probability, and to simulate the effect of changing the dose regimen. Methods Structural time-to-event models for dropouts (not because of a lack of efficacy) and seizures were developed using data from 883 adult patients newly diagnosed with epilepsy and experiencing focal or generalized ...

Population Pharmacokinetics of Cladribine in Patients with Multiple Sclerosis

Purpose The aims of this study were to characterize the concentration–time course of cladribine (CdA) and its main metabolite 2-chloroadenine (CAde), estimate interindividual variability in pharmacokinetics (PK), and identify covariates explaining variability in the PK of CdA. Methods This population PK analysis was based on the combined dataset from four clinical studies in ...

Pharmacokinetics of Rytary®, An Extended-Release Capsule Formulation of Carbidopa–Levodopa

Parkinson’s disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors, is the most effective and widely used therapeutic agent in the treatment of PD. ...

Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach

Background and Objective Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. Methods In a randomized, controlled, crossover trial, 12 healthy ...

A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults with Type 1 Diabetes

Background Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation aiming to mimic the fast endogenous prandial insulin release more closely than currently available insulin products. In a post hoc analysis of pooled data from six clinical pharmacology trials, the pharmacological characteristics of faster aspart and IAsp were compared. Methods The ...

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects

Background and Objective Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. The aim of the present study was to characterize the pharmacokinetics and exposure–response relationship of oral LSD. Methods We analyzed pharmacokinetic data from two published placebo-controlled, double-blind, cross-over studies using oral administration of LSD 100 and 200 ...

Clinical Pharmacokinetics and Pharmacodynamics of Pazopanib: Towards Optimized Dosing

Pazopanib is an inhibitor of the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, fibroblast growth factor receptor and stem cell receptor c-Kit, and has been approved for the treatment of renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib are complex and are characterized by pH-dependent solubility, large ...

Successful Use of [14C]Paracetamol Microdosing to Elucidate Developmental Changes in Drug Metabolism

Background We previously showed the practical and ethical feasibility of using [14C]-microdosing for pharmacokinetic studies in children. We now aimed to show that this approach can be used to elucidate developmental changes in drug metabolism, more specifically, glucuronidation and sulfation, using [14C]paracetamol (AAP). Methods Infants admitted to the intensive care unit ...

Population Pharmacokinetic Model and Pharmacokinetic Target Attainment of Micafungin in Intensive Care Unit Patients

Objective To study the pharmacokinetics of micafungin in intensive care patients and assess pharmacokinetic (PK) target attainment for various dosing strategies. Methods Micafungin PK data from 20 intensive care unit patients were available. A population-PK model was developed. Various dosing regimens were simulated: licensed regimens (I) 100 mg daily; (II) 100 mg daily with 200 mg ...