Desmopressin/indomethacin combination efficacy and safety in renal colic pain management: A randomized placebo controlled trial.

INTRODUCTION: Renal colic is a prevalent cause of abdominal pain in the emergency department. Although non-steroidal anti-inflammatory drugs and opioids are used for the treatment of renal colic, some adverse effects have been reported. Therefore, desmopressin -a synthetic analogue of vasopressin- has been proposed as another treatment choice. In the present study, indomethacin in combination with nasal desmopressin was compared with indomethacin alone in the management of renal colic. METHODS: Included in the study were 124 patients with initial diagnosis of renal colic and randomized to receive indomethacin suppository (100 mg) with either desmopressin intranasal spray (4 puffs, total dose of 40 micrograms) and or placebo intranasal spray. RESULTS: All the included patients were finally diagnosed with renal colic. There was no difference between the two groups in pain at the baseline (p = 0.4) and both treatments reduced pain successfully (p < 0.001). There was no significant difference between the two groups in pain reduction (p = 0.35). CONCLUSIONS: While there was significant pain reduction in both patients groups, pain reduction of NSAIDs (e.g. indomethacin) in renal colic, does not significantly improve when given in combination with desmopressin.

Implementation of transmission NIR as a PAT tool for monitoring drug transformation during HME processing.

The aim of the work reported herein was to implement process analytical technology (PAT) tools during hot melt extrusion (HME) in order to obtain a better understanding of the relationship between HME processing parameters and the extruded formulations. For the first time two in-line NIR probes (transmission and reflectance) have been coupled with HME to monitor the extrusion of the water insoluble drug indomethacin (IND) in the presence of Soluplus (SOL) or Kollidon VA64 hydrophilic polymers. In-line extrusion monitoring of sheets, produced via a specially designed die, was conducted at various drug/polymer ratios and processing parameters. Characterisation of the extruded transparent sheets was also undertaken by using DSC, XRPD and Raman mapping. Analysis of the experimental findings revealed the production of molecular solutions where IND is homogeneously blended (ascertained by Raman mapping) in the polymer matrices, as it acts as a plasticizer for both hydrophilic polymers. PCA analysis of the recorded NIR signals showed that the screw speed used in HME affects the recorded spectra but not the homogeneity of the embedded drug in the polymer sheets. The IND/VA64 and IND/SOL extruded sheets displayed rapid dissolution rates with 80% and 30% of the IND being released, respectively within the first 20min.

A kinetic study of the polymorphic transformation of nimodipine and indomethacin during high shear granulation.

The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a two-dimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol(-1) from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.

Determination of indomethacin in plasma by micellar electrokinetic chromatography with UV detection for premature infants with patent ducts arteriosus.

A simple and selective micellar electrokinetic chromatography (MEKC) is described for determination of indomethacin in plasma. Plasma proteins are precipitated by acetonitrile. An aliquot of supernatant was evaporated and reconstituted with Tris buffer for MEKC analysis. The separation of indomethacin was performed at 25 degrees C using a background electrolyte consisting of Tris buffer (30 mM; pH 8.0) with 100 mM sodium octanesulfonate (SOS) as an anionic surfactant. Under this condition, a good separation with high efficiency and short analysis time is achieved. Several parameters affecting the separation of indomethacin were studied, including pH and concentrations of the Tris buffer and SOS. The linear range of the method for the determination of indomethacin was over 0.3-10.0 microg/mL; the detection limit (signal-to-noise ratio=3; injection 0.5 psi 5s) was 0.1 microg/mL. The proposed method for determination of indomethacin in premature infants with patent ducts arteriosus has been demonstrated.

A study to determine the efficacy and safety of tenoxicam versus piroxicam, diclofenac and indomethacin in patients with osteoarthritis: a meta-analysis.

OBJECTIVE: To obtain a better quantitative and qualitative estimate of the effect of tenoxicam (Tx) compared to piroxicam (Px), diclofenac (Dcl) and indomethacin (Ind) in the treatment of osteoarthritis (OA). METHODS: Relevant studies were identified using computerized Medline search, manual search of cited references and correspondence with investigators, colleagues and the manufacturer of Tx. Once the studies were selected and chosen on the basis of predetermined methodologic criteria, the required data were extracted by 2 authors, independently. Eighteen studies met the required eligibility criteria. Meta-analyses were undertaken on 12 studies of Tx vs Px, 3 studies of Tx vs Dcl, and 2 studies of Tx vs Ind. Efficacy was measured in 2 ways: (1) physician global rating scale and (2) pain scale. Safety was measured in 3 ways: (1) physician global rating scale, (2) number of patients with adverse events, and (3) dropouts due to adverse events. RESULTS: The following findings of the meta-analysis were statistically significant: In Tx vs Px comparisons, efficacy-(1), safety-(1) and safety-(3) were all better with Tx; in Tx vs Ind comparisons, safety-(1) and safety-(2) were better with Tx. All other findings showed no statistically significant differences between Tx and the comparison drug. CONCLUSIONS: Compared to Px, Tx performs better on physician assessment of efficacy and tolerability, but the other comparisons remain inconclusive. Compared to Dcl, there appears not to be a difference. Compared to Ind, Tx is safer.

Worldwide experience with etodolac (Lodine) 300 mg b.i.d. in the treatment of osteoarthritis.

Worldwide experience with the conventional formulation of etodolac (300 mg b.i.d.) was reviewed in 12 randomized, double-blind, parallel-group studies in patients with osteoarthritis (OA) of the hip or knee. The studies were conducted in 13 countries at 59 sites, and 1289 patients were enrolled. The results of 9 comparative and 3 placebo-controlled clinical studies were examined to compare the efficacy and safety of etodolac versus piroxicam, naproxen, indomethacin, indomethacin sustained-release (SR), and diclofenac SR. Efficacy assessments were made at pretreatment screening, baseline, and every 2 weeks thereafter during treatment until study completion up to 4, 6, or 8 weeks. The primary efficacy assessments were the patient's and physician's global evaluations, pain intensity and night pain, or joint tenderness and walking pain. Safety was assessed with reference to study events, reports of laboratory results, and vital signs measurements. Patients in all active treatment groups showed prompt response to therapy. According to the physicians' global evaluation, at least 64% of all etodolac-treated patients and 62% of all active-reference preparation-treated patients had improved by the end of the study. Similar results were seen in the patients' global evaluation. All of the study drugs were well tolerated. Eight (8%) percent of the etodolac-treated patients withdrew because of study events. The proportions of patients treated with active reference preparations and placebos who withdrew because of study events ranged from 3% to 18%.(ABSTRACT TRUNCATED AT 250 WORDS)