Use of drugs with pharmacogenomics (PGx)-based dosing guidelines in a Danish cohort of persons with chronic kidney disease, both on dialysis and not on dialysis: Perspectives for prescribing optimization.

Aim: The objective of this registry study is to assess the utilization of pharmacogenomic (PGx) drugs among patients with chronic kidney disease (CKD).

Methods: This study was a retrospective study of patients affiliated with the Department of Nephrology, Aalborg University Hospital, Denmark in 2021. Patients diagnosed with CKD were divided into CKD without dialysis and CKD with dialysis.

Oral absorption of oxycodone in patients with short bowel syndrome.

Background: Short bowel syndrome is a disorder with several complications such as malnutrition and failure of drug therapy. Treatment with opioids is needed in many patients, and oral medication is preferred. However, optimal dosing is a difficult task as current guidelines are based on an intact gastrointestinal tract.

Creatinine-Based Renal Function Estimates and Dosage of Postoperative Pain Management for Elderly Acute Hip Fracture Patients.

Many analgesics and their metabolites are renally excreted. The widely used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-estimated glomerular filtration rate (eGFR) equations are not developed for use in the elderly, while the recent Berlin Initiative Study (BIS), Full Age Spectrum (FAS), and Lund-Malmö revised (LMR) equations are. This observational study investigated differences between creatinine-based eGFR equations and how the choice of equation influences dosage of analgesics in elderly (≥70 years) patients admitted with acute hip fracture.

Healthcare professionals' agreement on clinical relevance of drug-related problems among elderly patients.

Background Disagreement among healthcare professionals on the clinical relevance of drug-related problems can lead to suboptimal treatment and increased healthcare costs. Elderly patients with chronic non-cancer pain and comorbidity are at increased risk of drug related problems compared to other patient groups due to complex medication regimes and transition of care. Objective To investigate the agreement among healthcare professionals on their classification of clinical relevance of drug-related problems in elderly patients with chronic non-cancer pain and comorbidity.

Analysis of opioid consumption in clinical trials: a simulation based analysis of power of four approaches.

Inconsistent trial design and analysis is a key reason that few advances in postoperative pain management have been made from clinical trials analyzing opioid consumption data. This study aimed to compare four different approaches to analyze opioid consumption data. A repeated time-to-event (RTTE) model in NONMEM was used to simulate clinical trials of morphine consumption with and without a hypothetical adjuvant analgesic in doses equivalent to 15-62% reduction in morphine consumption.

Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study.

The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect.

A Pharmacokinetic-Pharmacodynamic Model of Morphine Exposure and Subsequent Morphine Consumption in Postoperative Pain.

Purpose: To characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation.

Methods: Dose, formulation and time of morphine administration was available from a published study in 63 patients receiving intravenous, oral immediate release or oral controlled release morphine on request after hip surgery. The PK-PD relationship between predicted exposure of morphine and morphine consumption was modeled using repeated time to event (RTTE) modeling in NONMEM.

Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon.

Objective: Opioid therapy is associated with altered secretion and motility of the gut. The relative contribution of decreased secretion to the development of opioid-induced constipation remains unknown.

Materials And Methods: Twenty-five healthy males were treated with oxycodone for 5 d in a placebo-controlled, randomised cross-over design.

Repeated Time-to-event Analysis of Consecutive Analgesic Events in Postoperative Pain.

Background: Reduction in consumption of opioid rescue medication is often used as an endpoint when investigating analgesic efficacy of drugs by adjunct treatment, but appropriate methods are needed to analyze analgesic consumption in time. Repeated time-to-event (RTTE) modeling is proposed as a way to describe analgesic consumption by analyzing the timing of consecutive analgesic events.

Methods: Retrospective data were obtained from 63 patients receiving standard analgesic treatment including morphine on request after surgery following hip fracture.

Exploratory survey study of long-term users of nicotine replacement therapy in Danish consumers.

Background: Long-term use of nicotine replacement therapy (NRT) has been approved in several countries for smokers who are unable or unwilling to quit smoking. However, information on basic characteristics, degree of nicotine dependence, health status and contentment with long-term use of NRT is scarce. The aim of this study was to collect information on the characteristics of long-term NRT users, having used NRT for at least 12 months, reasons for, and contentment with, their continued use of NRT including reasons for wishing to quit or sustain use and an estimation of their degree of nicotine dependence.

A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain.

Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can be used to quantify dose-response relationships for the population as well as interindividual and interoccasion variability. Additionally, relevant covariates for population subgroups that deviate from the typical population can be identified and help clinicians in dose optimisation.

Objective markers of the analgesic response to morphine in experimental pain research.

Introduction: In experimental pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect of morphine on three objective pharmacodynamic markers (pupil diameter, prolactin concentration and resting electroencephalography (EEG)) and compare the changes from placebo with subjective analgesia on experimental muscle pain for convergent validation.

Population pharmacokinetics of morphine and morphine-6-glucuronide following rectal administration--a dose escalation study.

Introduction: To safely and effectively administer morphine as liquid formulation via the rectal route, a thorough understanding of the pharmacokinetics is warranted. The aims were: (1) to develop a population pharmacokinetic model of liquid rectal morphine and morphine-6-glucoronide (M6G), (2) to simulate clinically relevant rectal doses of morphine and (3) to assess the tolerability and safety.

Material And Methods: This open label, dose escalation, four-sequence study was conducted in 10 healthy males.

Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models.

The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomised, double-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin and muscle.

Survey of patient and physician assessment of a compliance reminder device in the treatment of hypertension.

Low compliance to therapeutic regimens can have serious impact on patient health. A variety of technologies such as tablet dispensers and reminders has been developed to improve compliance. The aim of this study was to assess the acceptance of patients and physicians with regard to the functions and usefulness of a reminder device.

Translational pain research: evaluating analgesic effect in experimental visceral pain models.

Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can be achieved through standardized experimental human pain models.

Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model.

Analgesia from most opioids is mediated by mu receptors located mainly in the central nervous system. Previous studies have shown a different pharmacological profile of oxycodone in respect to visceral analgesia. This study investigated if morphine and oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with respect to delay between opioid blood concentration and analgesia.

A comparative study of oxycodone and morphine in a multi-modal, tissue-differentiated experimental pain model.

Visceral pain can be difficult to treat with classical mu-opioid agonists and it has been suggested to use opioids with distinct pharmacological profiles. In animal experiments, oxycodone has shown different effects compared to morphine, and clinical observations have shown that oxycodone may occasionally be superior to, e.g.