British journal of clinical pharmacology
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Br J Clin Pharmacol · Apr 2017
Randomized Controlled TrialPharmacokinetics and pharmacodynamics of a new highly concentrated intranasal midazolam formulation for conscious sedation.
To evaluate the pharmacokinetics, pharmacodynamics, nasal tolerance and effects on sedation of a highly concentrated aqueous intranasal midazolam formulation (Nazolam) and to compare these to intravenous midazolam. ⋯ This study demonstrates the nasal tolerance, safety and efficacy of Nazolam. When considering the preparation time needed for obtaining venous access, conscious sedation can be achieved in the same time span as needed for intravenous midazolam. Nazolam may offer important advantages in conscious sedation.
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Br J Clin Pharmacol · Feb 2017
Randomized Controlled Trial Comparative StudyThorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects.
The D2 /D3 antagonist amisulpride has shown promising efficacy against postoperative nausea and vomiting (PONV) at low doses. We investigated whether intravenous amisulpride has an effect on the QTc interval in a formal Thorough QT study (TQT). ⋯ Amisulpride has a plasma concentration-dependent effect on the QTc interval. The proposed therapeutic dose for management of PONV does not lead to a prolongation of QTcF above the threshold of regulatory concern, while such effect could not be excluded for the supratherapeutic dose.
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Br J Clin Pharmacol · Sep 2016
Randomized Controlled TrialPharmacokinetics of ixazomib, an oral proteasome inhibitor, in solid tumour patients with moderate or severe hepatic impairment.
The aim of the present study was to characterize the pharmacokinetics of the oral proteasome inhibitor, ixazomib, in patients with solid tumours and moderate or severe hepatic impairment, to provide posology recommendations. ⋯ In patients with moderate/severe hepatic impairment, unbound and total systemic exposures of ixazomib were 27% and 20% higher, respectively, vs. normal hepatic function. A reduced ixazomib starting dose of 3 mg is recommended for patients with moderate or severe hepatic impairment.
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Br J Clin Pharmacol · Apr 2016
Randomized Controlled TrialThe haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.
The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. ⋯ I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.
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Br J Clin Pharmacol · Mar 2016
Randomized Controlled TrialInvestigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach.
Olodaterol, a novel β2-adrenergic receptor agonist, is a long-acting, once-daily inhaled bronchodilator approved for the treatment of chronic obstructive pulmonary disease. The aim of the present study was to describe the plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers by population pharmacokinetic modelling and thereby to infer its pulmonary fate. ⋯ The plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers were adequately described. The key finding was that a high proportion of the pulmonary bioavailable fraction had an extended pulmonary residence time. This finding was not expected based on the physicochemical properties of olodaterol.