European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Nov 2007
Randomized Controlled Trial Comparative StudyLevocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.
To conduct a thorough QT study of levocetirizine, a non-sedating antihistamine, in accordance with International Conference on Harmonisation (ICH) E14 guidance. ⋯ Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic (5 mg) and supra-therapeutic (30 mg) doses on cardiac repolarisation.
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Eur. J. Clin. Pharmacol. · Oct 2007
Digoxin and mortality in atrial fibrillation: a prospective cohort study.
The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study showed that rhythm-control treatment of patients with atrial fibrillation (AF) offered no survival advantage over a rate-control strategy. In a subgroup analysis of that study, it was found that digoxin increased the death rate [relative risk (RR) = 1.42), but it was suggested that this may have been attributable to prescription of digoxin for patients at greater risk of death, such as those with congestive heart failure (CHF). No study has investigated a priori the effect of digoxin on mortality in patients with AF. This study aimed to address this question. ⋯ The results suggest that long-term therapy with digoxin is an independent risk factor for death in patients with AF without CHF.
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Eur. J. Clin. Pharmacol. · Sep 2007
Randomized Controlled TrialSerum and cerebrospinal fluid morphine pharmacokinetics after single doses of intravenous and intramuscular morphine after hip replacement surgery.
To compare the time course of morphine and metabolite concentrations in serum and cerebrospinal fluid (CSF) after intravenous and intramuscular administration after surgery. ⋯ The uptake of morphine to the CSF was consistently higher after IV administration than after IM already after 10 min. The higher CSF concentration may be caused by an initially higher morphine blood/CSF gradient following IV morphine injection. The pharmacokinetic findings are compatible with a more rapid and extensive initial effect of IV morphine compared with IM.
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Eur. J. Clin. Pharmacol. · Aug 2007
Randomized Controlled TrialPharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers.
After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers. ⋯ The pharmacokinetic profile of M6G after oral administration was confirmed and with the presence of M3G and morphine in plasma after oral administration of M6G, proof seems to be found of the constant and prolonged absorption of M6G. The K(M6G_abs)/K(M6G_M6G) ratio of 10 indicates that the second absorption peak of M6G consists of approximately 10 times more absorbed M6G than reglucuronidated M6G. However, further studies are required to determine the precise kinetics of the second absorption peak.