Disease relevance of Lorcam

• Data from preliminary clinical trials suggest that lornoxicam is as effective as the opioid analgesics morphine, pethidine (meperidine) and tramadol in relieving postoperative pain following gynaecological or orthopaedic surgery, and as effective as other NSAIDs after oral surgery [1].
• Lornoxicam was also as effective as other NSAIDs in relieving symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute sciatica and low back pain [1].
• The results of the baculovirus expression system showed that CYP2C9.3 gives higher K(m) and lower V(max) values for lornoxicam 5'-hydroxylation than does CYP2C9 [2].
• Evaluation of chronic oral toxicity and carcinogenic potential of lornoxicam in rats [3].
• CONCLUSION: In these patients with severe sepsis, we found intravenous lornoxicam to exert no effect on haemodynamic and biochemical parameters, cytokine levels, or patient outcomes [4].

High impact information on Lorcam

• Clinical pharmacokinetics of lornoxicam. A short half-life oxicam [5].
• Lornoxicam is eliminated following biotransformation to 5'-hydroxy-lornoxicam, which does not undergo enterohepatic recirculation [5].
• Substantial concentrations of lornoxicam are attained in synovial fluid, the proposed site of action in chronic inflammatory arthropathies [5].
• This randomised, double-blind, placebo controlled trial compared the analgesic efficacy and tolerability of intramuscular (IM) injections of lornoxicam (4, 8, 16 and 20 mg) with morphine (10 and 20 mg) and placebo in 252 patients with mainly moderate to severe pain following surgical removal of an impacted mandibular third molar [6].
• RESULTS: Lornoxicam 8 mg b.d. caused significantly less mucosal injury than naproxen 500 mg b.d. in the stomach/duodenal bulb, as well as in the mid/distal duodenum [7].

Chemical compound and disease context of Lorcam

• OBJECTIVE: To compare the efficacy and tolerability of lornoxicam and diclofenac in the treatment of patients with osteoarthritis (OA) over 12 weeks and to assess the efficacy and tolerability of lornoxicam over a followup period of 40 weeks [8].
• Parecoxib vs. lornoxicam in the treatment of postoperative pain after laparoscopic cholecystectomy: a prospective randomized placebo-controlled trial [9].
• Analgesic efficacy and safety of lornoxicam quick-release formulation compared with diclofenac potassium: randomised, double-blind trial in acute low back pain [10].
• CONCLUSION: In clinic, we can use lornoxicam to treat postoperative pain effectively and with less adverse reactions compared with fentanyl [11].

Biological context of Lorcam

• The effects of allelic variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) on lornoxicam 5'-hydroxylation were studied using the corresponding variant protein expressed in baculovirus-infected insect cells and human liver microsomes of known genotypes of CYP2C9 [2].
• In a subsequent clinical study, the AUC of lornoxicam was increased by 1.9-fold and its oral clearance (CL/F) decreased by 44% in three CYP2C9*1/*13 subjects, compared with CYP2C9*1/*1 individuals [12].
• These results suggest that lornoxicam is an alternative to morphine when administered by PCA for the treatment of moderate to severe postoperative pain [13].
• CONCLUSION: Lornoxicam may cause gastrointestinal and renal side effects without oxidative stress [14].
• To examine enzymatic activity of the CYP2C9*13 allele, kinetic parameters for lornoxicam 5'-hydroxylation were determined in COS-7 cells transiently transfected with pcDNA3.1 plasmids carrying wild-type CYP2C9*1, variant CYP2C9*3, and CYP2C9*13 cDNA [12].

Anatomical context of Lorcam

• Lornoxicam 5'-hydroxylation was also determined in liver microsomes of 12 humans genotyped for the CYP2C9 gene (*1/*1, n = 7; *1/*2, n = 2; *1/*3, n = 2; *3/*3, n = 1) [2].
• PURPOSE: To compare efficacy and patient outcome of wound infiltration with ropivacaine, lornoxicam, or their combination for control of pain following thyroid surgery [15].
• Using the serum pepsinogen I as a parameter for the integrity of the gastric mucosa, this suggests good gastric tolerance of lornoxicam [16].

Associations of Lorcam with other chemical compounds

• CONCLUSIONS: The addition of lornoxicam to lidocaine for intravenous regional anaesthesia shortens the onset of sensory and motor block, decreases tourniquet pain and improves postoperative analgesia without causing any side effect [17].
• No clinically relevant effect of lornoxicam intake on acenocoumarol pharmacokinetics and pharmacodynamics [18].
• Opposite effects of lornoxicam co-administration on phenprocoumon pharmacokinetics and pharmacodynamics [19].
• One hundred and twenty-two patients scheduled for primary elective knee arthroscopy in general anaesthesia were randomised to either a NSAID (lornoxicam) or a selective cox-II-inhibitor (rofecoxib) postoperatively [20].
• METHODS: We studied the effect of short-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) on faecal calprotectin shedding in two randomized crossover studies, with treatment regimens of indomethacin or naproxen for 14 days in the first study (n = 16) and lornoxicam or naproxen for 7 days in the second study (n = 18) [21].

Gene context of Lorcam

• The apparent affinity of lornoxicam was high for CYP2C9, but negligible for CYP3A4 and CYP2D6 [22].
• In stimulated monocytic cells (THP-1), lornoxicam showed a marked inhibition of IL-6 formation (IC50 54 microM) while the formation ofTNF-alpha, IL-1beta and IL-8 was only moderately affected [23].
• The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro [23].
• In contrast lornoxicam and meloxicam, which demonstrated activity against COX-2, have revealed smaller partition capacity in liposomes/water systems together with a higher ability to change the membrane fluidity and surface potential [24].
• RESULTS: Lornoxicam 5'-hydroxylation displayed single enzyme Michaelis-Menten kinetics, with a KM of 3.6 mu mol center dot l-1 and a Vmax of 2.6 nmol center dot h-1 center dot mg-1 microsomal protein [22].

Analytical, diagnostic and therapeutic context of Lorcam

• A comparison of patient-controlled analgesia with lornoxicam versus morphine in patients undergoing lumbar disk surgery [13].
• BACKGROUND: The aim of the study was to evaluate the effect of lornoxicam (L) on sensory and motor block onset time, tourniquet pain, and postoperative analgesia, when added to lidocaine in intravenous regional anaesthesia (IVRA) [17].
• The analgesic efficacy and tolerability of lornoxicam (Xefo; Nycomed Pharma A/S, Roskilde, Denmark), a new nonsteroidal antiinflammatory drug, was compared with that of morphine in a double-blind, randomized, parallel-group study of 96 patients with at least moderate pain after lumbar microsurgical discectomy [13].
• The plasma concentrations of lornoxicam and 5'-hydroxylornoxicam were determined by HPLC method [25].
• METHODS: In an open crossover study, six healthy male volunteers received racemic acenocoumarol (10 mg) orally without/with lornoxicam co-administration (8 mg twice daily) [18].

References