British Journal of Clinical Pharmacology - Volume 73 Issue 2 (February 2012)

1. Editors' report, November 2011

Date: Jan 06, 2012, Pages: 159-160

2. What do clinical pharmacologists do? A questionnaire survey of senior UK clinical pharmacologists

Date: Jan 06, 2012, Pages: 161-169

Since the discipline expanded during 1970–1990, the number of UK consultant clinical pharmacologists has fallen. This paper describes the results of a questionnaire survey of the work patterns of 53 UK consultant clinical pharmacologists, including 35 (66%) employed by universities and 13 (25%) employed by the National Health Service (NHS). The range of activities undertaken includes: teaching medical students and others the principles of...

3. Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited

Date: Jan 06, 2012, Pages: 170-174

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The rhizome of the Pacific kava plant (Piper methysticum) contains as its active constituents numerous kavalactones known for their relaxing properties. Kavalactones are found in aqueous, acetonic and ethanolic extracts of the kava rhizomes. These kava extracts are consumed worldwide and used for recreational purposes as well as to treat general anxiety. Kava use is associated with...

4. Positron emission tomography molecular imaging for drug development

Date: Jan 06, 2012, Pages: 175-186

Human in vivo molecular imaging with positron emission tomography (PET) enables a new kind of ‘precision pharmacology’, able to address questions central to drug development. Biodistribution studies with drug molecules carrying positron‐emitting radioisotopes can test whether a new chemical entity reaches a target tissue compartment (such as the brain) in sufficient amounts to be pharmacologically active. Competition studies, using a...

5. Pre‐hypertension: how low to go and do drugs have a role?

Date: Jan 06, 2012, Pages: 187-193

People with pre‐hypertension (high blood pressure but below the conventional threshold for intervention with antihypertensive drugs) undoubtedly have increased risk of cardiovascular and other complications. However, the vast majority has low absolute risk and whether treatment would be beneficial is uncertain. While pharmacotherapy has attractions from a public health perspective, clinicians and crucially those with pre‐hypertension...

6. Junior doctors prescribing: enhancing their learning in practice

Date: Jan 06, 2012, Pages: 194-202

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • A large proportion of medical graduates do not feel prepared for practice. • Prescribing is one of the biggest steps up from being a student to practising as a doctor. WHAT THIS STUDY ADDS • The lack of preparedness of graduates for practice is related to a lack of exposure and preparation for clinical practice. Preparedness may...

7. Assessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double‐blind, placebo‐ and positive‐controlled thorough QT study

Date: Jan 06, 2012, Pages: 203-209

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Drugs interacting with the hERG potassium channel are associated with a prolongation of the QT interval, which can lead to life‐threatening arrhythmias such as torsades de pointes. • Early prokinetic agents, such as cisapride, display poor selectivity for their target receptor, 5‐HT4, also interacting with hERG channels and, as a consequence, have a poor safety and...

8. Single dose pharmacokinetics, pharmacodynamics, tolerability and safety of BAY 60–5521, a potent inhibitor of cholesteryl ester transfer protein

Date: Jan 06, 2012, Pages: 210-218

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of cholesterol esters from the cardioprotective high density lipoprotein cholesterol (HDL‐C) to the proatherogenic low density lipoprotein cholesterol (LDL‐C) and very low density lipoprotein cholesterol (VLDL‐C) leading to lower concentrations of HDL‐C but raising the concentrations ...

9. Prediction of a potentially effective dose in humans for BAY 60–5521, a potent inhibitor of cholesteryl ester transfer protein (CETP) by allometric species scaling and combined pharmacodynamic and physiologically‐based pharmacokinetic modelling

Date: Jan 06, 2012, Pages: 219-231

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of cholesteryl esters from the atheroprotective high density lipoprotein (HDL) to the proatherogenic low density lipoprotein cholesterol (LDL) and very low density lipoprotein cholesterol (VLDL) leading to lower concentrations of HDL but raising the concentrations of proatherogenic ...

10. Pharmacokinetics, adverse effects and tolerability of a novel analogue of human pancreatic polypeptide, PP 1420

Date: Jan 06, 2012, Pages: 232-239

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Human pancreatic polypeptide (hPP) is a natural pancreatic hormone that suppresses appetite after meals. • When exogenous hPP is given to healthy human volunteers, it causes a reduction in food intake. • PP 1420 is a longer acting analogue of hPP that has been developed as a novel treatment for obesity. WHAT THIS STUDY ADDS ...

11. Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate

Date: Jan 06, 2012, Pages: 240-247

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • High dose methotrexate (HDMTX) is the most effective drug in treating primary central nervous system lymphoma (PCNSL). • While interoccasion variability of MTX elimination is moderate, interindividual variability is considerable and unpredictable. • MTX dose intensity is important in patients with PCNSL to allow for an optimal clinical outcome. ...

12. Prediction and evaluation of fetal toxicity induced by NSAIDs using transplacental kinetic parameters obtained from human placental perfusion studies

Date: Jan 06, 2012, Pages: 248-256

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in full‐term pregnant women leads to fetal or neonatal toxicity. However, the differences in fetal toxicity among NSAIDs remain to be fully investigated. • Therefore, the ability to predict fetal toxicity of NSAIDs quantitatively at full‐term pregnancy would be of clinical value. WHAT...

13. CYP2C8 but not CYP3A4 is important in the pharmacokinetics of montelukast

Date: Jan 06, 2012, Pages: 257-267

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The elimination of montelukast occurs mainly via metabolism and, according to its product information, CYP3A4 and 2C9 are the main metabolizing enzymes in vitro. • Recent studies, however, suggest that CYP2C8 may have a role in the metabolism of montelukast. WHAT THIS STUDY ADDS • The CYP3A4 inhibitor itraconazole...

14. Metabolic capabilities of cytochrome P450 enzymes in Chinese liver microsomes compared with those in Caucasian liver microsomes

Date: Jan 06, 2012, Pages: 268-284

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The mean catalytic activities of CYP1A2, CYP2A6, CYP2D6, CYP2E1 and CYP3A4 in human liver microsomes (HLM) of Japanese origin were found to be lower than the corresponding mean values of Caucasian HLM, but the distribution patterns of data in these studies were not well addressed. • Interindividual variations in metabolic activities of Chinese HLM...

15. Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol‐induced hepatotoxicity

Date: Jan 06, 2012, Pages: 285-294

WHAT IS ALREADY KNOWN ON THIS SUBJECT • Paracetamol hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. • Relatively little is known regarding the impact of staggered overdose pattern or delayed hospital presentation upon subsequent mortality or need for emergency liver transplantation. WHAT THIS STUDY ADDS • Staggered paracetamol...