European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Apr 2018
Comparative StudyImpact of ritonavir dose and schedule on CYP3A inhibition and venetoclax clinical pharmacokinetics.
Venetoclax is a selective BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). It is predominately metabolized by cytochrome P450 (CYP) 3A. The study objective was to determine the effect of different dosage regimens of ritonavir, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax in 20 healthy subjects. ⋯ After completion of the dose ramp-up, venetoclax dose reductions of at least 75% are recommended when administered concomitantly with strong CYP3A inhibitors to maintain venetoclax exposures within the established therapeutic window for CLL treatment.
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Eur. J. Clin. Pharmacol. · Mar 2018
Comparative StudyInter-rater reliability of STOPPFrail [Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy] criteria amongst 12 physicians.
STOPPFrail is an explicit tool, developed by Delphi consensus, to assist physicians with deprescribing medications in frail older adults with poor survival prognosis. This study aimed to determine the inter-rater reliability (IRR), amongst physicians, of STOPPFrail application. ⋯ IRR of STOPPFrail criteria between physicians, practising in different specialties, is substantial, despite no prior knowledge of the criteria.
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Eur. J. Clin. Pharmacol. · Mar 2018
Randomized Controlled Trial Clinical TrialNo major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA.
Methylenedioxymethamphetamine (MDMA, ecstasy) is used recreationally and frequently leads to sympathomimetic toxicity. MDMA produces cardiovascular and subjective stimulant effects that were shown to partially depend on the norepinephrine transporter (NET)-mediated release of norepinephrine and stimulation of α1-adrenergic receptors. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the NET gene (SLC6A2) may explain interindividual differences in the acute stimulant-type responses to MDMA in humans. ⋯ Genetic polymorphisms of the SLC6A2 gene weakly moderated the acute cardiovascular response to MDMA in controlled studies and may play a minor role in adverse cardiovascular events when MDMA is used recreationally.
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Eur. J. Clin. Pharmacol. · Mar 2018
Multicenter Study Observational StudyEffectiveness of biosimilar filgrastim vs. original granulocyte colony-stimulating factors in febrile neutropenia prevention in breast cancer patients.
The purpose of this study is to describe the effectiveness of biosimilar filgrastim and original granulocyte colony-stimulating factors (G-CSFs), lenograstim and pegfilgrastim, in febrile neutropenia (FN) prevention in breast cancer patients receiving docetaxel/doxorubicin/cyclophosphamide (TAC) as adjuvant/neoadjuvant treatment and to analyze their treatment patterns. ⋯ An abbreviated 5-day course of biosimilar filgrastim provided optimal primary prophylaxis against FN post-chemotherapy TAC in patients with breast cancer. The clinical relevance of the highest FN incidence in the lenograstim cohort needs further attention.
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Eur. J. Clin. Pharmacol. · Mar 2018
Randomized Controlled Trial Comparative StudyAn evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis.
Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. ⋯ If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and Evodial® appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode.