2016
DOI: 10.4236/pp.2016.712055
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<i>In Vivo</i> Interaction of Morphine and Diclofenac

Abstract: The number of studies on possible pharmacokinetic interactions between opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used in combination for the treatment of chronic pain, is limited. In rats, the major metabolic pathway of morphine is glucuronidation to morphine-3-glucuronide (M3G) by UDP-glucuronosyltransferase. In this study, we investigated the influence of diclofenac (NSAID) on the formation of M3G in vitro using rat liver tissue homogenates. Competitive inhibitio… Show more

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Cited by 3 publications
(11 citation statements)
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“…The goal of the present study was to evaluate the effects of some antifungals, benzodiazepines, and non-steroidal anti-inflammatory drugs (NSAIDs), on the phase II metabolic profile of morphine, and, in turn, on the reliability of the analytical strategies currently adopted by WADA-accredited anti-doping laboratories to detect the abuse of morphine by the athletes. In particular, we have extended the investigation reported by previous studies [44][45][46][47][48][49]…”
supporting
confidence: 70%
See 2 more Smart Citations
“…The goal of the present study was to evaluate the effects of some antifungals, benzodiazepines, and non-steroidal anti-inflammatory drugs (NSAIDs), on the phase II metabolic profile of morphine, and, in turn, on the reliability of the analytical strategies currently adopted by WADA-accredited anti-doping laboratories to detect the abuse of morphine by the athletes. In particular, we have extended the investigation reported by previous studies [44][45][46][47][48][49]…”
supporting
confidence: 70%
“…This leads to the formation of 2 metabolites, with pronounced differences in terms of biological activity, clearance, and toxicity: morphine-3-glucuronide (M3G, 50%-65%) and morphine-6-glucuronide (M6G, 5%-10%). [24][25][26][27][28][29][30][31][32][33][34][35][36] Analytical (eg, enzymatic hydrolysis), [37][38][39][40][41] physiological (eg, genetic polymorphism) 42 or non-physiological (eg, drug-drug interaction) factors [43][44][45][46][47][48][49] were reported to interfere with morphine determination in urine. Concerning, specifically, drug-drug interaction, experimental evidence indicates the ability of several agents (eg, antidepressants, antifungals) to significantly alter the activity of the enzymes involved in the principal metabolic pathways of morphine, with a consequent increase of its plasma concentration and decrease of the urinary levels of its metabolites.…”
mentioning
confidence: 99%
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“…We previously showed that glucuronidation of morphine is not inhibited even when diclofenac, which strongly inhibits UGT activity in vitro, is administered in combination with morphine in vivo (7). In that study, glucuronidation of morphine was similar between mice treated with either diclofenac or vehicle, despite a decrease in UGT activity due to inflammation.…”
Section: Changes In Relative Protein Levels Of Atp-binding Cassettementioning
confidence: 84%
“…Male Lewis rat liver microsomes were prepared as previously described (7). Briefly, tissues were minced and rinsed in ice-cold homogenate buffer (0.1 M Tris-HCl, 0.1 M KCl, 1 mM EDTA, pH 7.4) and homogenized in three volumes of 100 mM phosphate buffer (pH 7.4) containing 0.25 M sucrose.…”
Section: 9%; Aa 639%) and The Expression Of Atp-binding Cassette mentioning
confidence: 99%