Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mefenamic acid is a nonsteroidal anti-inflammatory drug commonly used in analgesia. The use of this drug has been implicated in several cases of nephrotoxicity including acute renal failure and tubulointerstitial nephritis. One theory of drug-induced tubulointerstitial nephritis is that the drug or a derivative of the drug becomes irreversibly bound to certain sites in renal tissue and an immune response is directed against the hapten-host conjugate. Previous studies have shown that in humans the nonsteroidal anti-inflammatory drug mefenamic acid is metabolized by both phase I enzymes and the phase II enzyme family UDP-glucuronosyltransferase. Indeed, three glucuronides were identified and isolated from human urine by semipreparative HPLC after oral administration of mefenamic acid. This study focuses on mefenamic acid glucuronide and further characterizes this acyl glucuronide in terms of stability and its ability to bind irreversibly to proteins. Stability studies of mefenamic acid glucuronide in aqueous buffer highlighted the relative stability of this acyl glucuronide at physiological pH. The half-life at 37 degrees C, pH 7.4, was 16.5 +/- 3.1 hr, which is considerably longer than those reported for many acyl glucuronides. The degradation of mefenamic acid glucuronide was accelerated under alkaline conditions, decreasing the half-life to 5 +/- 1.6 hr at pH 8.0. Mefenamic acid glucuronide, although extremely stable in buffer at physiological pH, was found to bind irreversibly to human serum albumin in vitro. Irreversible binding to cellular proteins in culture was also evident with the addition of mefenamic acid to the heterologous Chinese hamster lung fibroblast cell line V79 expressing the human UDP-glucuronosyltransferase isoenzyme UGT1*02. This binding was directly related to glucuronide formation, because irreversible binding was not evident in the untransfected cell line V79.
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PMID:Reactivity of mefenamic acid 1-o-acyl glucuronide with proteins in vitro and ex vivo. 886 17

A comparison of the efficacy of Myprodol, a combination analgesic (Ibuprofen, Paracetamol and Codeine phosphate) and Ponstan (Mefenamic acid) was undertaken in a randomised double blind trial of 52 patients who underwent surgical removal of impacted or unerupted teeth. Pain scores were measured for patients pre- and post operatively by means of a visual analogue scale and data was analysed using the BMPD package on the ISM main frame computer at the Medical Research Council. The results indicated that although Myprodol and Ponstan were equally adequate and well tolerated in the control of post operative dental pain, Myprodol exceeded Ponstan in duration of analgesia and in the degree of pain intensity control experienced by the patient.
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PMID:Comparison of the safety and efficacy of a combination analgesic Myprodol and Ponstan in the treatment of dental pain. 951 22