Search

Background: Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation. Results: There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively. Conclusion: In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

No therapeutic ranges linking drug concentrations of apixaban and rivaroxaban to clinical outcomes have been defined. We investigated whether direct oral anticoagulant (DOAC) concentrations among patients admitted to hospital with symptoms of stroke differed between those later verified to suffer an ischaemic cerebrovascular event (stroke or transient ischaemic attack) and those having other diagnoses (control group). Serum concentrations in 102 patients on DOAC for atrial fibrillation (84%) and thromboembolic disease (16%) were measured within 24 h of the acute event, employing ultra‐high performance liquid chromatography with tandem mass spectrometry. We converted all concentrations to standardized trough levels. DOAC concentrations were lower in the 64 patients with verified ischaemic cerebrovascular event than in the 30 controls, 255 ± 155 versus 329 ± 144 nmol/L (p = 0.029), despite no statistically significant difference in self‐reported adherence and daily dosages. Calculated concentrations were 5.4–596 nmol/L (median = 229 nmol/L) in the ischaemic stroke group and 41–602 nmol/L (median = 316 nmol/L) in controls. CHA2DS2‐VASc score was significantly higher in the ischaemic stroke group than in controls (4.9 ± 1.6 versus 4.1 ± 1.7; p = 0.007). These results may suggest that patients with high cerebrovascular risk might benefit from higher DOAC levels than those with a lower risk. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Changes in gastrointestinal physiology following bariatric surgery may affect the pharmacokinetics of drugs. Data on the impact of bariatric surgery on drugs used for attention‐deficit/hyperactivity disorder (ADHD) are limited.In patients treated with ADHD medication and undergoing bariatric surgery, serial drug concentrations were measured for 24 h preoperatively and one, six and 12 months postoperatively. Primary outcome was change in area under the concentration‐time curve from 0 to 24 h (AUC0–24), with other pharmacokinetic variables as secondary outcomes.Eight patients treated with lisdexamphetamine (n = 4), dexamphetamine (n = 1), methylphenidate (n = 1) and atomoxetine (n = 2) were included. In total, 409 samples were analysed. Patients underwent sleeve gastrectomy (n = 5) and Roux‐en‐Y gastric bypass (n = 3). AUC0–24 and Cmax of dexamphetamine increased after surgery in those using the prodrug lisdexamphetamine. There was no clear‐cut reduction in tmax postoperatively. For ritalinic acid and atomoxetine, no changes in AUC0–24 were observed, but for atomoxetine, a higher Cmax and a shorter tmax were observed postoperatively.Bariatric surgery may increase the systemic exposure of dexamphetamine after intake of lisdexamphetamine. Patients using lisdexamphetamine should be followed with regard to adverse drug reactions after bariatric surgery, and, if available, therapeutic drug monitoring should be considered. [ABSTRACT FROM AUTHOR]

The article presents information on a study which develops an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for detection of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine samples, collected from sexual assault victims . The results suggest that EtG/EtS analysis may help in determining possible alcohol involvement in such cases.