[A case of effective readministration of itraconazole for recurrent allergic bronchopulmonary aspergillosis].
A simple and sensitive high performance liquid chromatography method using UV detection (HPLC-UV) for the determination of meloxicam in human plasma was developed and validated. After extraction with diethyl ether, the chromatographic separation of meloxicam was carried out using a reverse phase Sunfire C18 column (150 mm x 4.6mm, 5 microm) with a mobile phase of acetonitrile-20mM potassium hydrogen phosphate (40:60, v/v, pH 3.5) and UV detection at a wavelength of 355 nm. The flow rate of mobile phase was 1.2 ml/min and the retention time of meloxicam and internal standard, piroxicam, was found to be 11.6 and 6.3 min, respectively. The calibration curve was linear within the concentration range, 10-2400 ng/ml (r2>0.9999). The lower limit of quantification was 10 ng/ml. This method improved the sensitivity for the quantification of meloxicam in plasma using a HPLC-UV. The mean accuracy was 98-114%. The coefficient of variation (precision) in the intra- and inter-day validation was 1.6-4.3 and 2.4-7.3%, respectively. The pharmacokinetics of meloxicam was evaluated after administering an oral dose of 15 mg to 11 healthy Korean subjects. The AUCinf, Cmax, tmax and t1/2 were 42.4+/-13.2 microg h/ml, 1445.7+/-305.5 ng/ml, 4.1+/-0.3h and 22.0+/-4.9h, respectively.
Meloxicam (MLX) was formulated as a 0.3% hydroxypropylcellulose (Klucel) gel. The effect of four different combinations of co-solvents (ethanol, glycol-PEG-400, propylene glycol, and water) on MLX permeability was determined in vitro throughout isopropyl myristate (IPM)-saturated cellulose membranes. The gel consisting of 2.5% Klucel, propylene glycol, ethanol, and water (1:1:1) showed superior permeability properties and it was selected as the base-gel to investigate the effect of three levels of the penetration enhancers: dimethylsulfoxide (1, 5, and 10% DMSO), tween20 (1, 2, and 5% TW20), oleic acid (0.4, 1, and 5% OA), and menthol (1, 2.5, and 5% MT). In vitro permeability was determined throughout IPM-saturated cellulose membranes and human cadaver skin. DMSO and TW20 did not improve permeability of MLX compared to the control gel at any of the levels tested. Menthol produced a statistically significant (P<0.001), dose proportional increase in MLX flux with a peak at 5% (2.43+/-0.47 microg/cm2/h). Conversely, addition of OA peaked at 1% but decreased at the higher level (5%). There was no significant difference between the MLX amount recovered in stratum corneum and dermis across the different formulations tested. These findings show that the 0.3% MLX gel formulation containing 5% menthol can possibly deliver therapeutically relevant doses of MLX.
To investigate the renal protective effect of specfic cyclooxygenase 2 inhibitor meloxicam on the renal of diabetic nephropathy rats.
Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain, inflammation, and fever by inhibiting cyclooxygenases (COXs). Nonsteroidal anti-inflammatory drugs selective for COX-2 were developed to inhibit the major enzymatic source of the prostaglandins that mediate pain and inflammation while sparing COX-1-derived prostaglandins that contribute dominantly to gastric cytoprotection. Indeed, such purpose-designed COX-2 inhibitors reduced the incidence of serious gastrointestinal adverse effects when compared with traditional NSAIDs; however, they confer a small but absolute cardiovascular hazard. The hazard might also extend to traditional NSAIDs, which are relatively selective for COX-2, such as diclofenac, meloxicam, and etodolac. The occurrence of complications and the therapeutic responses to individual NSAIDs may vary substantially from patient to patient. Exploitation of detectable variability in the biochemical response to NSAIDs may offer an approach to the personalization of the management of risk and benefit.
COX inhibition prevented ABL in this experimental periodontal disease model. MLX displays similar efficacy and less gastric damage than IND. MLX may provide a better risk/benefit ratio in the treatment of human periodontitis than non-selective COX inhibitors.
This study adds to the evidence that pain management when disbudding is beneficial for calf productivity as well as calf welfare.
Postoperative pain and its management following fistulation surgery in cattle are poorly understood. The purpose of this study was to compare 2 nonsteroidal antiinflammatory drugs (NSAID) as potential postoperative pain management treatments following the first stage of a 2-stage fistulation surgery. A randomized complete block design trial was conducted in dry Holstein cows (n=10) following fistulation surgery. Ketoprofen (3mg/kg of body weight i.m.) was administered on the day of surgery and 24 h later, whereas meloxicam (0.5 mg/kg of body weight s.c.) was administered once only on the day of surgery. Outcomes evaluated at 0, 2, 9, 24, 26, and 33 h postsurgery were heart rate, respiration rate, rectal temperature, and infrared temperature around the surgical site. Outcomes evaluated on the day of surgery and d 1 following surgery and compared with the average for the 4d before surgery were lying activity (total lying time, total time spent lying on the left side, and percentage of time lying on the left side) and feed intake. A difference was observed in dry matter intake on d 1 but this effect was not different on d 0 compared with presurgical averages. A difference was observed in time spent lying on the left side and a difference was observed in heart rate following the first stage of fistulation surgery compared with presurgical averages. The infrared temperature readings around the surgical site were significantly greater in the hours following surgery compared with presurgical averages. The respiration rate increased over time after 24h postsurgery compared with presurgical values. Although it was clear that the surgery is painful, the drug effects were more difficult to explain. On d 0 and 1, the meloxicam-treated cows ate 3 kg more but spent 101 min/d less time lying on their left side compared with ketoprofen-treated cows. The first stage of a 2-stage fistulation surgery was considered painful based on changes in heart rate, respiration rate, infrared temperature readings, dry matter intake, and time spent lying on the left side. It is clear that left flank surgery is painful and that NSAID can improve outcomes associated with that pain, but we cannot make recommendations as to which NSAID to choose based on these results.