Clin Pharmacokinet
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To examine morphine metabolite serum concentrations in neonates undergoing venoarterial extra corporeal membrane oxygenation (ECMO) and to quantify clearance differences between these neonates and those subjected to noncardiac major surgery. ⋯ Formation clearance to M3G, the predominant metabolite, is reduced during the first 10 days of ECMO. Elimination clearance of M3G and M6G is related to creatinine clearance. ECMO flow had a small effect on metabolite clearance. Higher flows were associated with decreased formation clearances, possibly reflecting illness severity. Dopamine dose reflected decreased renal clearance.
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Randomized Controlled Trial
A population pharmacokinetic/pharmacodynamic analysis of regadenoson, an adenosine A2A-receptor agonist, in healthy male volunteers.
The aims of this study were to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of regadenoson (CVT-3146) in healthy, male volunteers. ⋯ The pharmacokinetics and the effects of regadenoson on heart rate were successfully described using pharmacokinetic/pharmacodynamic modelling. The lack of a correlation between the model estimates and various baseline patient demographics supports unit-based dose administration of regadenoson.
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Review
Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation.
The ability to deliver safe and effective moderate sedation is crucial to the ability to perform invasive procedures. Sedative drugs should have a quick onset of action, provide rapid and clear-headed recovery, and be easy to administer and monitor. A number of drugs have been demonstrated to provide effective sedation for outpatient procedures but since each agent has its own limitations, a thorough knowledge of the available drugs is required to choose the appropriate drug, dose and/or combination regimen for individual patients. ⋯ AQUAVAN injection (fospropofol disodium), a phosphorylated prodrug of propofol, is an investigational agent possessing a unique and distinct pharmacokinetic and pharmacodynamic profile. Compared with propofol emulsion, AQUAVAN is associated with a slightly longer time to peak effect and a more prolonged pharmacodynamic effect. Advances in the delivery of sedation, including the development of new sedative agents, have the potential to further improve the provision of moderate sedation for a variety of invasive procedures.
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Randomized Controlled Trial Comparative Study
Comparison of equivalent doses of fentanyl buccal tablets and arteriovenous differences in fentanyl pharmacokinetics.
The fentanyl buccal tablet (FBT) is designed to enhance the rate and extent of fentanyl absorption through the buccal mucosa. ⋯ Despite small differences in C(max) and AUC(infinity) (on average 12% and 13%, respectively), FBT administered as four 100 microg tablets simultaneously compared with one 400 microg tablet did not meet the criteria for bioequivalence. An increased surface area exposure with four tablets compared with one tablet may account for the slightly higher maximum concentrations observed with four 100 microg tablets. A substantially higher C(max) was reached earlier in the arterial than in the venous circulation.
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Lamellar liposome technology has been used for several decades to produce sustained-release drug formulations for parenteral administration. Multivesicular liposomes are structurally distinct from lamellar liposomes and consist of an aggregation of hundreds of water-filled polyhedral compartments separated by bi-layered lipid septa. The unique architecture of multivesicular liposomes allows encapsulating drug with greater efficiency, provides robust structural stability and ensures reliable, steady and prolonged drug release. ⋯ Contingent on the specific formulation and manufacturing process, agents were released over a period of hours to weeks as reflected by a 2- to 400-fold increase in elimination half life. Published data further suggest that the encapsulation process preserves bioactivity of agents as delicate as proteins and supports the view that examined multivesicular liposomes were non-toxic at studied doses. The task ahead will be to examine whether the beneficial structural and pharmacokinetic properties of multivesicular liposome formulations will translate into improved clinical outcomes, either because of decreased drug toxicity or increased drug efficacy.