British journal of clinical pharmacology
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Br J Clin Pharmacol · Jul 2012
Correlation of paired toxic plasma and saliva paracetamol concentrations following deliberate self-poisoning with paracetamol.
• Paracetamol is commonly used in deliberate self poisoning (DSP) and this requires blood sampling to refine risk assessment. If saliva concentrations agreed with plasma concentrations, then this could support the development of non-invasive testing. Our pilot work supports this hypothesis, but was largely confined to nontoxic concentrations. ⋯ The agreement between the indications for treatment of paracetamol DSP based on plasma and saliva paracetamol concentrations extends into the toxic range, but with slightly lower agreement. Saliva may hold promise as a non-invasive method to risk stratify paracetamol poisoning.
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Br J Clin Pharmacol · May 2012
Randomized Controlled TrialAssessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects.
AIMS To evaluate the pharmacology and tolerability of PF-04457845, an orally available fatty acid amide hydrolase-1 (FAAH1) inhibitor, in healthy subjects. ⋯ PF-04457845 was well tolerated at doses exceeding those required for maximal inhibition of FAAH1 activity and elevation of fatty acid amides.
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Br J Clin Pharmacol · May 2012
Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects.
To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. ⋯ Methadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6.
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Br J Clin Pharmacol · May 2012
Biography Historical ArticleDavid Grahame Grahame-Smith: clinical pharmacologist. 1933-2011.
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Br J Clin Pharmacol · Apr 2012
Population pharmacokinetics of ciclosporin in haematopoietic allogeneic stem cell transplantation with emphasis on limited sampling strategy.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The population pharmacokinetics and limited sampling strategies for ciclosporin monitoring have been extensively studied in renal and liver transplant recipients. Little is known about the pharmacokinetics of ciclosporin in patients undergoing haematopoietic allogeneic stem cell transplantation (HSCT). • It is anticipated that there is a difference in pharmacokinetics in patients after kidney or liver transplantation compared with patients undergoing stem cell transplantation, because of mucositis and interacting drugs (e.g. fluconazole). • Data on the pharmacokinetics of ciclosporin and the relationship between its systemic exposure, as reflected by the area under the curve (AUC), and the biological effect as graft vs. host-disease (GVHD) prophylaxis and graft vs. tumour (GVT) response are scarce in patients after HSCT. WHAT THIS STUDY ADDS • A pharmacokinetic model was developed for orally and intravenously administered ciclosporin, enabling an adequate estimate of the systemic exposure of ciclosporin in patients after HSCT. ⋯ Two selected LSS two time point equations and all selected three and four time point equations predicted de all AUC(0,12 h) within 15% bias and prediction. CONCLUSIONS The i.v. and oralcurves were best described with a two compartment model with first-order absorption with lag time. With the Bayesian estimators from this model, the area under the concentration-time curve in HSCT patients taking fluconazole can be estimated with only three blood samples (0, 2, 3 h) with a bias of 1% and precision of 4%.