Human cytochrome P450 (CYP) is a superfamily of hemoproteins which oxidize a number of endogenous compounds and xenobiotics. The human CYP2C subfamily consists of four members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 and CYP2C19 are important drug-metabolizing enzymes and together metabolize approximately 20% of therapeutically used drugs. Forty-two allelic variants for CYP2C9 and 34 for CY...

Salvinorin A is an unregulated potent hallucinogen isolated from the leaves of Salvia divinorum. It is the only known non-nitrogenous kappa-opioid selective agonist, and rivals synthetic lysergic acid diethylamide (LSD) in potency. The objective of this study was to characterize the in vitro transport, in vitro metabolism, and pharmacokinetic properties of Salvinorin A. The transport characteri...

INTRODUCTION Given the promising advantages of upper extremity home-based programmes in children with cerebral palsy (CP), a systematic review of the available literature on this topic is warranted. The purpose of the systematic review described in this protocol is to investigate currently available home-based occupational therapy and physiotherapy programmes regarding both their feasibility an...

Research investigating CYP2C8 as a drug-metabolizing enzyme has gained momentum over the past few years. CYP2C8 is estimated to oxidatively metabolize approximately 5% of therapeutically prescribed drugs. It is polymorphically expressed, and several single nucleotide polymorphisms have been identified with varying effects on the clearance of CYP2C8 substrates. However, the human liver expressio...

This paper describes the development and validation of a measure of strategies used by patients to cope with chronic pain, the Chronic Pain Coping Inventory (CPCI). A 104-item measure of pain coping responses and 3 measures of functioning were completed by 176 chronic pain patients. Two-week retest data were provided by 111 of these patients. Item and scale analyses resulted in a 65-item measur...

Using selective cytochrome P450 (CYP) inhibitors and clinical concentrations (4 mM) of dapsone (DDS), we found a major contribution of CYP2C9 and little or no contribution (<10%) of CYP3A4 and CYP2E1 to dapsone N-hydroxylation (DDS-NHY) in human liver microsomes. Sulfaphenazole (2.16 mM) and tolbutamide (500 mM), selective inhibitors of CYP2C9 (or 2C8/9), inhibited DDS-NHY by 48 6 14 and 41 6 1...

Cytochromes P450 (P450s) are down-regulated in hepatocytes in response to inflammation and infection. This effect has been extensively studied in animal models, but significantly less is known about responses in humans and even less about responses in the absence of inducing agents. This article focuses on the effects of bacterial lipopolysaccaride (LPS), interleukin-6 (IL-6), tumor necrosis fa...

In mammals, Cytochrome P450 (CYP) enzymes are bound to membranes of the endoplasmic reticulum and mitochondria, where they are responsible for the oxidative metabolism of many xenobiotics as well as organic endogenous compounds. In humans, 57 isoforms were identified which are classified based on sequence homology. In the present work, we demonstrate the performance of a mass spectrometry-based...