lornoxicam and ampiroxicam

The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised.. To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease.. Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays.. Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P = 0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P = 0.018, respectively).. The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aryl Hydrocarbon Hydroxylases; Aspirin; Capsule Endoscopy; Case-Control Studies; Cytochrome P-450 CYP2C9; Diaphragm; Diclofenac; Double-Balloon Enteroscopy; Female; Humans; Intestinal Diseases; Intestine, Small; Male; Meloxicam; Middle Aged; Piroxicam; Polymorphism, Single Nucleotide; Risk Factors; Thiazines; Thiazoles

A high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique was developed for the simultaneous determination of five non-steroidal anti-inflammatory oxicam drugs (ampiroxicam, tenoxicam, piroxicam, meloxicam and lornoxicam) in human plasma. These five oxicam drugs and isoxicam (internal standard) were extracted from human plasma with an Oasis(®) MAX cartridge column and analysed on a Unison UK-C18 column (2.0 mm × 100 mm, 3 μm) with an acetonitrile:10mM formic ammonium buffer (pH 3.0) (50:50) mobile phase at 0.20 ml/min at 37°C. The analytes were detected using a tandem mass spectrometer, equipped with an electrospray ion source (ESI). The instrument was used in multiple-reaction-monitoring (MRM) mode. The extraction yields from a 200 μl human plasma sample (containing 10 ng of each drugs) with the Oasis(®) MAX cartridge column were 93.3-102.5%. The detection limits were 0.01-6.5 ng/ml (S/N=3). Our developed method is very useful for the simultaneous determination of five oxicam (non-steroidal anti-inflammatory) drugs in human plasma by LC/MS/MS.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chromatography, Liquid; Forensic Toxicology; Humans; Meloxicam; Molecular Structure; Piroxicam; Tandem Mass Spectrometry; Thiazines; Thiazoles