Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Aug 2011
ReviewSurrogate endpoints in randomized cardiovascular clinical trials.
Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. ⋯ Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints.
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Fundam Clin Pharmacol · Aug 2011
Clinical TrialRelationships between plasma concentrations of morphine, morphine-3-glucuronide, morphine-6-glucuronide, and intravenous morphine titration outcomes in the postoperative period.
Although intravenous morphine titration (IMT) is widely used to control moderate to severe postoperative pain, the relationships between plasma concentrations of morphine and its metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), and IMT outcomes in the postanesthesia care unit (PACU) have not been yet investigated. IMT was administrated as a bolus of 2 or 3 mg every 5 min. Titration was interrupted in case of pain relief (visual analog score ≤30), adverse events, sedation, or failure of morphine titration. ⋯ At the end of titration, there were no significant differences in morphine, M6G, M3G concentrations between sedated and nonsedated patients (32 vs. 42 ng/mL (P = 0.07), 38 vs. 45 ng/mL (P = 0.51), 300 vs. 342 ng/mL (P = 0.29), respectively), or patients with or without adverse events (40 vs. 41 ng/mL (P = 0.95), 37 vs. 46 ng/mL (P = 0.51), 287 vs. 340 ng/mL (P = 0.72), respectively). Our study demonstrated a lack of relationship between plasma concentrations or ratios of morphine, M3G, and M6G, with IMT outcomes in PACU. This result suggests that the kinetics of morphine and its metabolites have limited value for explaining clinical effects of morphine in this clinical setting.