British journal of clinical pharmacology
-
Br J Clin Pharmacol · Apr 2016
Clinical TrialParacetamol decreases steady-state exposure to lamotrigine by induction of glucuronidation in healthy subjects.
Patients receiving lamotrigine therapy frequently use paracetamol concomitantly. While one study suggests a possible, clinically relevant drug-drug interaction, practical recommendations of the concomitant use are inconsistent. We performed a systematic pharmacokinetic study in healthy volunteers to quantify the effect of 4 day treatment with paracetamol on the metabolism of steady-state lamotrigine. ⋯ Paracetamol statistically significantly induced steady-state lamotrigine glucuronidation, resulting in a 20% decrease in total systemic exposure and a 25% decrease in trough value of lamotrigine. This interaction may be of clinical relevance in some patients.
-
Flumazenil and naloxone are considered to be pharmacologically ideal antidotes. By competitive binding at the molecular target receptors, they are highly specific antagonists of two important drug classes, the benzodiazepines and opioids, respectively. ⋯ Yet only naloxone is widely used as a component of the 'coma cocktail', a sequence of empirical treatments to correct altered mental status, while experts discourage the use of flumazenil for such patients. This review contrasts the history, indications, published evidence and novel applications for each antidote in order to explain this disparity in the clinical use of these 'ideal' antidotes.
-
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.
-
Br J Clin Pharmacol · Mar 2016
ReviewCalcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies.
Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. ⋯ Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.