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These highlights are written on the historic day Britain decided to leave the EU. As the first non‐UK Editor of the British Journal of Clinical Pharmacology some reflection is in order. It gives some consolation that the ‘Brexit issue’ of BJCP contains work from groups from 17 different countries, 10 from the EU, and from three continents. Clearly, a British‐focused journals strategy would not be a productive strategy for BJCP.
Clinical science needs to be borderless and we will not be influenced by decisions in the political arena, so keep sending your good work from wherever you are. Even though your Editor‐in‐Chief may soon need a visa to visit the office, your papers will pass through without obstructions!
The great ESCAPE – a clinical pharmacologist's journey in stroke research
David J. P. Williams
In December David Williams gave the GSK lecture at Pharmacology 2015 and this paper is a condensation of that lecture that covered stroke research and care from the bench to the bedside and beyond into policy decisions. You can also listen to the lecture through https://www.youtube.com/watch?v=85zJl8uLLlY&index=1&list=PLxoEwD0mB8KqTqBs4xQeRUMIRbyQrPCWt
Injection site reactions after subcutaneous oligonucleotide therapy
Leonie van Meer, Matthijs Moerland, Jolie Gallagher, Martijn B. A. van Doorn, Errol P. Prens, Adam F. Cohen, Robert Rissmann and Jacobus Burggraaf
Antisense DNA molecules are perhaps the most specific of all medicines as they only bind to a particular stretch of DNA, with virtually total specificity. This theoretically should lead to a very low amount of off target side effects. Enter the innate immune system, unfortunately. The body has very aspecific defense mechanisms against free RNA in the circulation as this is normally caused by viral infections. Renal damage has been described and skin reactions on the site of injection, although they are described as benign, they can be disfiguring and long lasting. Leonie van Meer gives an overview of the state of knowledge about this unpleasant skin reaction that may be (one of) the Achilles heels of this promising form of therapy.
Acute p‐synephrine ingestion increases fat oxidation rate during exercise
Jorge Gutiérrez‐Hellín and Juan Del Coso
Losing weight is the ultimate aim of every sweating citizen ones meets in any park anywhere in the world. Would it not be nice if medicines existed that would make this happen faster. P‐Synepphrin is a rather undefined substance occurring in bitter oranges and preparations are sold as food supplements to increase fat burning. This may suggest to the average obese person that the layers of unsightly flab are burned away, but of course this is not the case. In this paper the authors do what should be done, experiment to see what goes on. The substance appeared to have effects on fat utilization during exercise. The tests derive this from the use of oxygen and production of CO2 so they did not see the fat go away. However, this is an important example of how the claims on so called food supplements should be approached experimentally. In principle this shift to fat utilization should improve endurance, so if you see a Spanish team eating a lot of bitter orange during the upcoming Tour de France you will know they read the right journal.
Pharmacokinetics of lamotrigine and its metabolite N‐2‐glucuronide: Influence of polymorphism of UDP‐glucuronosyltransferases and drug transporters
Daniela Milosheska, Bogdan Lorber, Tomaž Vovk, Matej Kastelic, Vita Dolžan and Iztok Grabnar
The antiepileptic lamotrigine (Lamictal) always draws my attention as I happen to be the individual giving the first dose ever to a human being, the Wellcome clinical pharmacologist Tony Peck, who led its development to the market.
We rapidly discovered that the clearance of the drug, which was known to be glucuronidated, was lower in subjects with Gilbert syndrome ‐ an abnormality in glucuronidation of bilirubin. This was in the days before measurement of metabolites was easy and molecular biology approachable. Daniela Milosheska now investigates these metabolic pathways with the techniques of today.
Pharmacokinetic/pharmacodynamic modelling of the antimalarial effect of Actelion‐451840 in an induced blood stage malaria study in healthy subjects
Andreas Krause, Jasper Dingemanse, Alexandre Mathis, Louise Marquart, Jörg J. Möhrle and James S. McCarthy
Development of new drugs for malaria is essential as this is still a major cause of death in the world and resistance is increasing. Experimental infection with malaria sounds frightening but can be done safely and gives great opportunities for quantitatively evaluating treatment effects of new medicines. Andreas Krause and colleagues give a beautiful example of how to do this, using a challenge test in healthy subjects and turning these findings into a mathematical model. Essential reading for anyone interested in how to develop an antimalarial drug rationally and quantitatively.
Adverse drug reactions caused by common drugs feature in the journal this month.
Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease
Christel Renoux, Sophie Dell'Aniello, Paul Khairy, Connie Marras, Shawn Bugden, Tanvir Chowdhury Turin, Lucie Blais, Hala Tamim, Charity Evans, Russell Steele, Colin Dormuth, Pierre Ernst and the Canadian Network for Observational Drug Effect Studies (CNODES) investigators
Renoux et al discuss the use of domperidone as an anti‐emetic in patients with Parkinson's disease, noting a higher chance of ventricular tachycardia and sudden cardiac death particularly in patients with a history of cardiovascular disease.
Evaluation of the risk of cardiovascular events with clarithromycin using both propensity score and self‐controlled study designs
Adrian A. Root, Angel Y. S. Wong, Yonas Ghebremichael‐Weldeselassie, Liam Smeeth, Krishnan Bhaskaran, Stephen J. W. Evans, Ruth Brauer, Ian Chi KeiWong, Vidya Navaratnam and Ian Douglas
Cardiovascular risk, this time associated with clarithromycin, is the subject of Root et al's report on patients treated for helicobacter pylori and subsequent risk of myocardial infarction. Despite a short term association, data shows that long term cardiac outcomes are no different.
Muscle rupture associated with statin use
Corine Ekhart, Loek de Jong, Liana Gross‐Martirosyan and Florence van Hunsel
Statins are the most widely prescribed drugs in the world and have been associated with a number of ADRs. Muscle rupture is described as a new edition to the list in Ekhart et al's review of pharmacovigilance reports from the Netherlands.
Peripheral vasoconstriction induced by β‐adrenoceptor blockers: a systematic review and a network meta‐analysis
Charles Khouri, Thomas Jouve, Sophie Blaise, Patrick Carpentier, Jean‐Luc Cracowski and Matthieu Roustit
Beta‐blockers are another commonly used group of medicines, generally avoided in patient intolerant to peripheral vasoconstriction. Khouri and colleagues present data suggesting that those beta‐blockers with intrinsic sympathomimetic properties may be better tolerated.
What influences persistence with medicines? A multinational discrete choice experiment of 2549 patients
Emily A. F. Holmes, Valerie L. Morrison and Dyfrig A. Hughes
Finally, Holmes et al give some additional insights into why patients do or do not persist with drug treatment, including the trade‐off between risks of ADRs and benefits.