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Background Morphine-6-glucuronide (M6G) is a strong µ-receptor agonist with higher affinity than morphine itself. It has been suggested that M6G contributes to the analgesic effect after administration of morphine, but the extent of its contribution remains unclear. Methods In order to elucidate the relative contribution of both drugs to the overall analgesic effect mediated by the µ-receptor, published data on µ-receptor binding, plasma protein binding, concentrations [preferably area under the concentration–time curve (AUC)] of morphine and M6G in blood or cerebrospinal fluid (CSF), or concentration ratios were used to calculate free CSF concentration corrected for receptor binding for each compound. To compare different routes of administration, free CSF concentrations of M and M6G corrected for potency were added and compared with oral administration. Results Based on AUC data, there is a major contribution of M6G to the overall analgesic effect; the mean contributions being estimated as 96.6%, 85.6%, 85.4%, and 91.3% after oral, s.c., i.v., and rectal administration of morphine, respectively. In patients with renal insufficiency, 97.6% of the analgesic effect is caused by M6G when morphine is given orally. Owing to accumulation of M6G over time in these patients, morphine may be regarded as a prodrug. Conclusions When administering morphine to patients, the analgesic effect is mainly caused by M6G instead of morphine itself, irrespective of the route of administration. Therefore, the patient's kidney function plays a key role in determining the optimal daily dose of morphine. [ABSTRACT FROM AUTHOR]

Aims: To test the in vivo activity of Cytochrome P450 (CYP) 2E1 in obese children vs. nonobese children, aged 11–18 years. Secondly, whether the activity of CYP2E1 in these patients is associated with NALFD, diabetes or hyperlipidaemia. Methods: Seventy children were divided into groups by body mass index (BMI) standard deviation score (SDS). All children received 250 mg oral chlorzoxazone (CLZ) as probe for CYP2E1 activity. Thirteen blood samples and 20‐h urine samples were collected per participant. Results: Obese children had an increased oral clearance and distribution of CLZ, indicating increased CYP2E1 activity, similar to obese adults. The mean AUC0–∞ value of CLZ was decreased by 46% in obese children compared to nonobese children. The F was was increased twofold in obese children compared to nonobese children, P < 0.0001. Diabetic biomarkers were significantly increased in obese children, while fasting blood glucose and Hba1c levels were nonsignificant between groups. Liver fat content was not associated with CLZ Cl. Conclusion: Oral clearance of CLZ was increased two‐fold in obese children vs. nonobese children aged 11–18 years. This indicates an increased CYP2E1 activity of clinical importance, and dose adjustment should be considered for CLZ. [ABSTRACT FROM AUTHOR]

Examines the toxicity of flecainide. Association of cardiac arrhythmias treatment with adverse drug reactions; Elimination of flecainide by urinary excretion and hepatic metabolism; Analysis on the kinetics of renal excretion of flecainide.