Interchangeability of generic drugs for subpopulations: Bioequivalence simulation from a nonparametric PK model of gabapentin generic drugs.

Unlabelled: Patients are often switched between generic formulations of the same drug, but in some cases generic interchangeability is questioned. For generic drugs to be approved, bioequivalence with the innovator drug should be demonstrated, but evidence of bioequivalence is not required in the intended patient population or relative to other approved generics.

Aim: We aim to identify pathophysiological pharmacokinetic subpopulations for whom there is a difference in comparative bioavailability compared to a healthy population.

Pharmacokinetics and Generic Drug Switching: A Regulator's View.

There appears to be a mismatch between the assumed therapeutic equivalence of generic drugs, their interchangeability, and reported clinical discomfort following generic drug use and drug switches. In this article, we describe why we are of the opinion that the current regulatory approach to the evaluation of generic drugs based on average bioequivalence is sufficient to expect therapeutic equivalence in the clinical setting. This has often been debated, specifically as adverse drug reactions related to generic drug switches are regularly reported.

Does Circadian Rhythm Affect the Pharmacokinetics of Once-Daily Tobramycin in Adults With Cystic Fibrosis?

Background: In the era of multiple daily dosing of systemic aminoglycosides, a circadian rhythm in the clearance of these vital antibiotics has been demonstrated in animals and healthy volunteers. Over the past decade, once-daily dosing regimens have been proved to be less nephrotoxic and were therefore adopted worldwide for most indications requiring treatment with an aminoglycoside. In this study, the effect of the time of administration on the pharmacokinetics of once-daily tobramycin in adults with cystic fibrosis (CF) experiencing a pulmonary exacerbation was investigated.

A limited sampling strategy to estimate exposure of once-daily modified release tacrolimus in renal transplant recipients using linear regression analysis and comparison with Bayesian population pharmacokinetics in different cohorts.

Purpose: Tacrolimus has a narrow therapeutic window. Measuring trough level (C) as surrogate for drug exposure (AUC) in renal transplant recipients has limitations. Therefore, limited sampling strategies (LSS's) have been developed.

Drug utilization in the Maastricht Study: A comparison with nationwide data.

Within the southern region of the Netherlands, the Maastricht Study is an on-going observational prospective population-based cohort study that focuses on the etiology of Type 2 diabetes mellitus (T2DM). Representativeness of the participating population is a crucial but often an unknown factor in population-based cohort studies such as the Maastricht Study. We therefore aimed to assess the representativeness of the study population by comparing drug utilization of the participants of the Maastricht Study with the general population of the Netherlands.

Commutability of proficiency testing material containing amitriptyline and nortriptyline: A study within the framework of the Dutch Calibration 2.000 project.

Background: External quality assessment schemes (EQAS) can provide important information regarding accuracy and comparability of different measurement methods if the sample matrices are composed of commutable material. The aim of this study was to assess the commutability of different matrices for the material used in an EQAS for amitriptyline and nortriptyline.

Methods: Proficiency testing material (PTM) and patient samples containing amitriptyline and nortriptyline were prepared, collected, pooled, and distributed to participating laboratories for analysis.

A Novel Ileocolonic Release Peppermint Oil Capsule for Treatment of Irritable Bowel Syndrome: A Phase I Study in Healthy Volunteers.

Introduction: Peppermint oil (PO) has been shown to reduce abdominal pain in patients with irritable bowel syndrome (IBS). PO is assumed to induce intestinal smooth muscle relaxation and desensitization of nociceptive nerve afferents. To increase colonic PO concentration, an ileocolonic release peppermint oil (IC-PO) capsule has been developed.

The use of incretins and fractures - a meta-analysis on population-based real life data.

The aim of the present study was to estimate the effect of incretins on fracture risk in the real-world situation by meta-analysis of the available population-based cohort data. Pubmed and Embase were searched for original articles investigating use of incretin agents, and fracture risk up to December 2015. Adjusted results were extracted and pooled by use of generic inverse variance methods, assuming a random-effects model.

Commutability of proficiency testing material containing tobramycin: a study within the framework of the Dutch Calibration 2.000 project.

Background: Results from external quality assessment schemes (EQASs) can provide information about accuracy and comparability of different measurement methods, provided that the material used in these schemes behave identical to patient samples among the different methods, a characteristic also known as commutability. The aim of this study was to assess the commutability of different matrices for the material used in an EQAS for tobramycin.

Methods: Proficiency testing material (PTM) and patient samples containing tobramycin were prepared, collected, pooled, and distributed to participating laboratories for analysis.

A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

Aims: The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance.

Methods: The study was designed as a retrospective reanalysis of existing studies. Nine replicate design bioequivalence studies representing six drug classes - i.

Use of Dipeptidyl-Peptidase-4 Inhibitors and the Risk of Pneumonia: A Population-Based Cohort Study.

Background: Dipeptidyl-peptidase-4 inhibitors (DPP4Is) are drugs for the treatment of type 2 diabetes mellitus (T2DM). There is increasing evidence that DPP4Is may result in suppression of the immune system and may increase the risk of infections such as pneumonia. Aim of this study was to evaluate the association between the use of DPP4Is and the risk of pneumonia in a population-based study.

Evaluation of Vancomycin Prediction Methods Based on Estimated Creatinine Clearance or Trough Levels.

Background: The aim of this study was to investigate whether vancomycin clearance (CLva) can be adequately predicted with CLva prediction methods. Additionally, other covariates influencing the CLva were investigated and predictivity of monitoring of only trough levels to 24-hour area under the curve (AUC24) was evaluated.

Methods: Routine vancomycin plasma levels were measured with a fluorescence polarization immunoassay.

Use of Glucagon-Like-Peptide 1 Receptor Agonists and Risk of Fracture as Compared to Use of Other Anti-hyperglycemic Drugs.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs that might have a potential beneficial effect on bone metabolism. Data on the effect of GLP-1 RAs and fracture risk are lacking. The aim of the present study was to investigate the association between the use of GLP-1 and the risk of fracture.

Use of dipeptidyl peptidase 4 inhibitors and fracture risk compared to use of other anti-hyperglycemic drugs.

Introduction: Dipeptidyl peptidase-4 inhibitors (DPP4-Is) are a new class of anti-hyperglycemic drugs which might have a potential beneficial effect on bone metabolism. Data on the effect of DPP4-I use and fracture risk is limited and conflicting. The aim of the present study was to investigate the association between use of DPP4-Is and fracture risk.

Investigation into the interchangeability of generic formulations using immunosuppressants and a broad selection of medicines.

Purpose: To date, the interchangeability of generic drugs has only been investigated for a limited number of medicines. The objective of this study was to investigate generic-generic drug interchangeability in a large subset of generic formulations in order to cover a broad spectrum of drugs.

Methods: Orally administered drugs for investigation in this study were selected using strict, predefined criteria, with the purpose to avoid bias.

Bone fracture risk is not associated with the use of glucagon-like peptide-1 receptor agonists: a population-based cohort analysis.

Glucagon-like Peptide-1 receptor agonists (GLP1-ra) are a relatively new class of anti-hyperglycemic drugs which may positively affect bone metabolism and thereby decrease (osteoporotic) bone fracture risk. Data on the effect of GLP1-ra on fracture risk are scarce and limited to clinical trial data only. The aim of this study was to investigate, in a population-based cohort, the association between the use of GLP1-ra and bone fracture risk.

Chronopharmacokinetics of once daily dosed aminoglycosides in hospitalized infectious patients.

Background: hospitalized patients with serious infections treated with aminoglycosides are at risk of developing nephrotoxicity. Previous clinical studies have shown that the pharmacokinetics of aminoglycosides in humans follow a circadian rhythm. Therefore, the time of administration could have important clinical implications with respect to the risk of developing aminoglycoside-associated nephrotoxicity in patients treated with once daily dosing regimens.

A Multilaboratory Commutability Evaluation of Proficiency Testing Material for Carbamazepine and Valproic Acid: A Study Within the Framework of the Dutch Calibration 2000 Project.

Background: Medical laboratories are required to participate in interlaboratory comparisons of the analyses they perform. The materials used in these comparisons need to be of sufficient quality so that the comparison provides a picture of the performances. One of the main characteristics of the testing material is commutability, which is the ability of a material to yield the same numerical relationships between results of measurements as those relationships obtained when the same procedures are applied to patient samples.

Vancomycin dosing in neutropenic patients.

Background: To compare vancomycin pharmacokinetic parameters in patients with and without neutropenia.

Methods: Patients ≥18 years admitted on general wards were included. Routinely vancomycin trough and peak plasma concentrations were measured with a fluorescence polarization immunoassay.

Design and prospective validation of a dosing instrument for continuous infusion of vancomycin: a within-population approach.

Introduction: The clinical application of continuous infusion (CoI) of vancomycin has gained interest in recent years. Since no international guidelines on initial dosing of vancomycin CoI exist, there is a need for methods to facilitate the switch from intermittent to continuous vancomycin dosing algorithms in clinically infected populations. Therefore, the aim of this study was to design and validate an a priori dosing schedule for CoI of vancomycin in clinical practice.

Use of dipeptidyl peptidase-4 inhibitors for type 2 diabetes mellitus and risk of fracture.

Introduction: Although patients with type 2 diabetes mellitus have an increased bone mineral density as compared to healthy patients, their risk of fracture is elevated. Incretins, new anti-diabetic drugs, may have a protective effect on bone mineral density. However, data on the effect of incretins on fracture risk are limited.

Is the standard dose of amoxicillin-clavulanic acid sufficient?

Background: The pharmacodynamic (PD) efficacy target of amoxicillin is 40% time above the minimal inhibition concentration (40%T > MIC). Recent studies of other antibiotics have shown that PD-efficacy targets are not always reached. The aim of this study was to evaluate the percentage of hospitalised patients, using amoxicillin/clavulanic acid intravenously (iv), that reach the pharmacodynamic efficacy target 40%T > MIC.