European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Jan 2014
Clinical TrialThe impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects.
Codeine is an analgesic drug acting on μ-opioid receptors predominantly via its metabolite morphine formed almost exclusively by CYP2D6. Genetic polymorphisms in CYP2D6 are associated with diminished pain relief and/or severe opioid side effects. In Chinese individuals, CYP2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the effect of this allele on the pharmacokinetics of codeine and its metabolites. ⋯ This study demonstrates that the CYP2D6*10 allele plays an important role in the pharmacokinetics of the O-demethylated metabolites of codeine after oral administration.
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Pregabalin is a novel GABA-analogue approved for the treatment of partial onset seizures, neuropathic pain, and general anxiety disorder. Pregabalin has been classified as a Schedule V drug with a low risk of inflicting abuse or addiction. However, some publications have indicated that pregabalin may have a potential for abuse among patients with past or current opiate addiction. Thus, we hypothesized that pregabalin might be abused by patients who were undergoing an opiate replacement therapy and never had an indication for taking pregabalin on medical grounds. ⋯ Our data suggest that pregabalin is liable to be abused among individuals with opiate dependency syndrome Thus, vigilance and caution are called for when patients with a past or current opiate dependency are exposed to treatment with pregabalin.
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Eur. J. Clin. Pharmacol. · Oct 2013
Meta AnalysisMeta-analyses of dose-exposure relationships for gabapentin following oral administration of gabapentin and gabapentin enacarbil.
Gabapentin exposure following administration of certain doses of gabapentin or its pro-drug gabapentin enacarbil has been previously reported in the literature, with variable results. ⋯ The meta-analyses addressed issues associated with between-study variability; and confirmed the highly non-linear nature of dose-exposure relationships for gabapentin and the essentially linear relationships for gabapentin enacarbil. The resulting models could be used to simulate exposure at any clinically relevant dose and bridge therapeutic dose range between the two drugs.
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Eur. J. Clin. Pharmacol. · Sep 2013
Comparative StudyIneffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care.
To determine whether treatment with nitrofurantoin in women with urinary tract infection (UTI) and renal impairment in primary care is associated with a higher risk of ineffectiveness and/or serious adverse events than in women without renal impairment. ⋯ Overall, the incidence density for ineffectiveness was 5.4 per 1,000 person-days, and moderate renal impairment was not associated with ineffective treatment [HR 1.1, 95 % confidence interval (CI) 0.74-1.51]. The overall incidence density for adverse events was 0.02 per 1,000 person-days. In patients with renal impairment (<50 ml/min/1.73 m²) the risk of pulmonary adverse events leading to hospitalization was significantly increased (HR 4.1, 95 % CI 1.31-13.09) CONCLUSIONS: Nitrofurantoin treatment was not associated with a higher risk of ineffectiveness in women with UTI and moderate renal impairment (30-50 ml/min/1.73 m²). However, we did find a significant association between renal impairment (<50 ml/min/1.73 m²) and pulmonary adverse events leading to hospitalization.
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Eur. J. Clin. Pharmacol. · Sep 2013
Clinical TrialGenetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain.
To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms. ⋯ By considering COMT, OPRM1, and UGT2B7 genotypes, as well as pharmacokinetic results, only COMT polymorphisms appear to be predictive of morphine need in postoperative pain therapy.