Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2− breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 × 4.6 mm, 2.6 µm) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors’ peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between −1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between −14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2− breast cancer.

To estimate the effect size of concomitant antiepileptic therapy on the concentrations of lamotrigine, a drug often prescribed in combination with other antiepileptic drugs (AED), which can act as enzyme inducers or inhibitors.A total of 304 patients ...

Background and Objectives: The purpose of this study was to compare the effect of topical bromfenac and dexamethasone on the intraocular concentration of interleukin 6 (IL-6) and incidence of pseudophakic cystoid macular oedema (PCME) after cataract surgery in patients with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: Ninety eyes of patients with mild-to-moderate NPDR that underwent phacoemulsification cataract surgery were divided into three groups. A detailed description of the clinical study protocol is described later in paper. In short, Group 1 received topical bromfenac (0.9 mg/mL), Group 2 dexamethasone (1 mg/mL), and Group 3 placebo, both preoperatively and postoperatively. Additionally, all patients received combined topical steroid and antibiotic drops (dexamethasone, neomycin and polymyxin B) 3 weeks postoperatively. On the day of the surgery, aqueous humour samples (0.1–0.2 mL) were obtained and IL-6 concentrations were analysed. Central foveal subfield thickness (CFT) measured using spectral-domain optical coherence tomography (SD-OCT) was analysed preoperatively and postoperatively. Results: There was no significant difference in IL-6 concentrations between groups. Postoperative CFT was significantly lower in the dexamethasone group compared to the placebo group. In addition, the correlation between IL-6 and CFT was statistically significant in the dexamethasone group. No patient developed PCME in any of the three groups. No adverse events were reported during the study. Conclusion: Topical bromfenac and dexamethasone have no significant effect on intraocular IL-6 concentration in patients with NPDR. Topical bromfenac is not more effective than topical dexamethasone in reducing postoperative CFT in patients with NPDR.

The ATP-binding cassette subfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is an efflux transporter expressed in key pharmacokinetic tissues and biological barriers. It regulates exposure to many endogenous compounds, drugs, and environmental toxins. Genetic variability in ABCG2 has been recognised as an important contributor to interindividual variability in drug response, especially in terms of efficacy and toxicity. This narrative review summarises current knowledge on the clinical relevance of ABCG2 genetic variants, with a focus on their effects on pharmacokinetics, adverse drug reactions and drug–drug–gene interactions, as well as their potential implementation in personalised therapy. A literature search was performed in PubMed, Scopus and the Clinical Pharmacogenomics Database (ClinPGx), with an emphasis on clinically relevant studies and available pharmacogenomic guidelines. The most investigated ABCG2 variant, c.421C>A (rs2231142; p.Gln141Lys), is consistently associated with reduced transporter activity and increased systemic exposure to several substrate drugs, including statins, allopurinol and anticancer agents, which may influence both treatment response and the risk of toxicity. Although growing evidence supports the clinical relevance of ABCG2 genotyping, its routine implementation remains limited. Integration of ABCG2 variability into polygenic models and clinical decision-support tools may further improve individualised treatment, particularly in patients with multimorbidity and polypharmacy.

Introduction. Polymorphism ABCG2 c.421C > A (rs2231142) results in a reduced activity of the important drug efflux transporter breast cancer resistance protein (BCRP/ABCG2). One study suggested that it may affect enterohepatic recirculation of mycophenolic acid (MPA). We evaluated the effect rs2231142 on steady-state exposure to MPA in renal transplant recipients. Methods. Consecutive, stable adult (age ≥ 16 years) renal transplant recipients on standard MPA-based immunosuppressant protocols (N = 68, 43 co-treated with cyclosporine, 25 with tacrolimus) underwent routine therapeutic drug monitoring after a week of initial treatment, and were genotyped for ABCG2 c.421C > A and 11 polymorphisms in genes encoding enzymes and transporters implicated in MPA pharmacokinetics. ABCG2 c.421C > A variant vs. wild-type (wt) patients were matched in respect to demographic, biopharmaceutic and genetic variables (full optimal combined with exact matching) and compared for dose-adjusted steady-state MPA pharmacokinetics (frequentist and Bayes [skeptical neutral prior] estimates of geometric means ratios, GMR). Results. Raw data (12 variant vs. 56 wt patients) indicated by around 40% higher total exposure (frequentist GMR = 1.45, 95%CI 1.10–1.91; Bayes = 1.38, 95%CrI 1.07–1.81) and by around 30% lower total body clearance (frequentist GMR = 0.66, 0.58–0.90; Bayes = 0.71, 0.53–0.95) in variant carriers than in wt controls. The estimates were similar in matched data (11 variant vs. 43 wt patients): exposure GMR = 1.41 (1.11–1.79) frequentist, 1.39 (1.15–1.81) Bayes, with 90.7% and 85.5% probability of GMR > 1.20, respectively; clearance GMR = 0.73 (0.58–0.93) frequentist, 0.71 (0.54–0.95) Bayes. Sensitivity analysis indicated high unsusceptibility of the estimates to unmeasured confounding. Conclusions. Loss-off-function polymorphism ABCG2 c.421C > A increases steady-state exposure to MPA in stable renal transplant patients.

Introduction: Brivaracetam belongs to antiepileptic drugs and due to the interindividual variability, therapeutic drug monitoring is recommended, especially when used in polytherapy and in patients with altered pharmacokinetics. The aim of this study is to develop and validate a high-performance liquid chromatography (HPLC) method with a diode array detector (HPLC-DAD) that is suitable for therapeutic monitoring of brivaracetam and assess method’s greenness. Materials and methods: High-performance liquid chromatography method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and Clinical and Laboratory Standards Institute (CLSI) guidelines. Preparation of serum samples was performed by liquid–liquid extraction using ethyl acetate:hexane (1:1) with chloramphenicol as internal standard. Separation was achieved using a 5 µm 4.6 × 250 mm C18 Shim-pack GIST column with the mobile phase consisting of a 50 mM phosphate buffer (pH = 4.5) and organic mixture of acetonitrile and methanol (8/3; v/v). Brivaracetam is quantified at 210 nm. AGREEprep was utilized for the method’s greenness scoring. Results: The developed HPLC-DAD method is linear over a concentration range of 0.25–20.00 µmol/L. Repeatability was lower than 7.20%, intermediate precision was lower than 8.30%, and within-laboratory precision was lower than 10.50%, except for the values at the lower limit of quantification (0.25 µmol/L) which were still below 20.00%. Bias was lower than ±10.60%. The method displays very high specificity at 210 nm. The result for method greenness was 0.4. Conclusions: The validation parameters were within the acceptance criteria of the ICH and CLSI guidelines. The developed method is simple, selective, reproducible, more sensitive than other published HPLC methods and suitable for the therapeutic drug monitoring of brivaracetam.