Basic Clin Pharmacol Toxicol
October 2024
The healthcare sector is a major contributor of greenhouse gas emissions, and reduction and proper sorting of healthcare waste is essential to achieve sustainable healthcare. This study aimed to characterize the quantity and composition of pharmaceutical waste from a major Danish hospital. Pharmaceutical waste was collected from Odense University Hospital, including departments located in both Odense and Svendborg.
View Article and Find Full Text PDFThis cross-sectional study investigates the occurrence of the prescribing cascade of antiemetic after hormone therapy.
View Article and Find Full Text PDFWe investigated the impact of genetic variants in OCT1 (SLC22A1) on morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) pharmacokinetics in adult patients scheduled for major surgery. Blood samples were taken before and 5, 10, 15, 30, 45, 60 and 90 min after a bolus of morphine (0.15 mg/kg).
View Article and Find Full Text PDFThe aim of the study was to investigate if there is a clinically relevant drug interaction between metformin and codeine. Volunteers were randomized to receive on four separate occasions: (A) orally administered metformin (1 g), (B) intravenously administered metformin (0.5 g), (C) five doses of tablet codeine 25 mg; the last dose was administered together with oral metformin (1 g), and (D) five doses of tablet codeine 25 mg; the last dose was administered together with metformin (0.
View Article and Find Full Text PDFAims: Recently a limited sampling strategy (LSS) for determination of metformin' pharmacokinetics was developed. The LSS utilizes the plasma concentration of metformin 3 and 10 hours after oral intake of a single dose to estimate the area under the concentration-time curve up to 24 hours (AUC ). The main purpose of this study was to support the feasibility of this strategy in a large prospective trial.
View Article and Find Full Text PDFPurpose: Largely based on case series, several drugs have been implicated in drug-induced restless legs syndrome (RLS) including selective serotonin reuptake inhibitors (SSRI). We aimed to assess the association between initiation of SSRIs and RLS in a self-controlled design.
Methods: We conducted a symmetry analysis, including Danish adults who filled in their first prescription of an SSRI in the period of 1997-2017 and initiated an RLS drug (quinine, ropinirole, pramipexole or rotigotine) 1 year prior to or after this date.
The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence base for drug-drug interactions between clarithromycin and currently marketed statins and to present management strategies for these drug combinations. We conducted a systematic literature review following PRISMA guidelines with English language studies retrieved from PubMed and EMBASE (from inception through March 2019).
View Article and Find Full Text PDFBasic Clin Pharmacol Toxicol
January 2019
Delta-9-tetrahydrocannabinol (THC), the main psychoactive cannabinoid in cannabis, may inhibit the cytochrome P450 enzyme CYP2C9. Consequently, cannabis use might infer a risk of drug-drug interaction with substrates for this enzyme, which includes drugs known to have a narrow therapeutic window. In this study, we describe a case report of a 27-year-old man treated with warfarin due to mechanical heart valve replacement who presented with elevated international normalized ratio (INR) value (INR = 4.
View Article and Find Full Text PDFMetformin pharmacokinetics (PK) is highly variable, and researchers have for years tried to shed light on determinants of inter-individual (IIV) and inter-occasion variability (IOV) of metformin PK. We set out to identify the main sources of PK variability using a semi-mechanistic model. We assessed the influence of subject characteristics, including seven genetic variants.
View Article and Find Full Text PDFBackground: Fracture risk is increased in individuals with type 2 diabetes (T2D). The pathophysiological mechanisms accentuating fracture risk in T2D are convoluted, incorporating factors such as hyperglycaemia, insulinopenia, and antidiabetic drugs. The objectives of this study were to assess whether different insulin regimens, metformin and rosiglitazone influence bone metabolism.
View Article and Find Full Text PDFPolycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. PCOS is associated with obesity, dyslipidaemia and insulin resistance, and metformin treatment may improve such metabolic features. The effect of genetic variants in key metformin transporters, their transcriptional regulators or in metformin target genes on metformin response in women with PCOS is unclear.
View Article and Find Full Text PDFUnlabelled: Metformin is the most widely prescribed oral antiglycemic drug, with few adverse effects. However, surprisingly little is known about its human biodistribution and target tissue metabolism. In animal experiments, we have shown that metformin can be labeled by C and that C-metformin PET can be used to measure renal function.
View Article and Find Full Text PDFAim: The aim was to develop and validate limited sampling strategy (LSS) models to predict the area under the plasma concentration-time curve (AUC) for metformin.
Methods: Metformin plasma concentrations (n = 627) at 0-24 h after a single 500 mg dose were used for LSS development, based on all subsets linear regression analysis. The LSS-derived AUC(0,24 h) was compared with the parameter 'best estimate' obtained by non-compartmental analysis using all plasma concentration data points.
The aim of this study was to examine the risk of early discontinuation of metformin as a proxy for intolerance, associated with use of drugs known to inhibit transporters involved in metformin distribution. We analysed all incident users of metformin in Denmark between 2000 and 2012 (n = 132,221) and in a cohort of US patients (n = 296,903). Risk of early discontinuation of metformin was assessed using adjusted logistic regression for 28 drugs putatively inhibiting metformin transporters and four negative controls.
View Article and Find Full Text PDFBasic Clin Pharmacol Toxicol
March 2016
The purpose of this study was to examine whether the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions: A: baseline; B: after 21 days of treatment with St.
View Article and Find Full Text PDFMetformin is the world's most commonly used oral glucose-lowering drug for type 2 diabetes, and this is mainly because it protects against diabetes-related mortality and all-cause mortality. Although it is an old drug, its mechanism of action has not yet been clarified and its pharmacokinetic pathway is still not fully understood. There is considerable inter-individual variability in the response to metformin, and this has led to many drug-drug interaction (DDI) studies of metformin.
View Article and Find Full Text PDFPurpose: The aim of the study was to determine the steady-state pharmacokinetics of metformin in healthy volunteers with different numbers of reduced-function alleles in the organic cation transporter 1 gene (OCT1).
Methods: The study was conducted as part of a randomized cross-over trial. Thirty-four healthy volunteers with known OCT1 genotypes (12 with two wild-type alleles, 13 with one and 9 with two reduced-function alleles) were included.
Aims: Our objective was to investigate the steady-state pharmacokinetic and pharmacodynamic interaction between the antidepressive herbal medicine St John's wort and the antidiabetic drug metformin.
Methods: We performed an open cross-over study in 20 healthy male subjects, who received 1 g of metformin twice daily for 1 week with and without 21 days of preceding and concomitant treatment with St John's wort. The pharmacokinetics of metformin was determined, and a 2 h oral glucose tolerance test was performed.
Background: A four-drug cytochrome P450 (CYP) phenotyping cocktail was developed to rapidly and safely determine CYP2D6, CYP2C19, CYP2C9 and CYP1A2 enzyme activity and phenotype.
Methods: The cocktail consisted of the single CYP phenotyping probes of 50 mg tramadol (CYP2D6), 20 mg omeprazole (CYP2C19), 25 mg losartan (CYP2C9) and 200 mg caffeine (CYP1A2) and was administered as a single oral dose. For enzyme activity measurements, urine was collected as 8 h post-administration and blood was sampled at 4 h.