Clin Pharmacokinet
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Controlled Clinical Trial
Mechanism-based pharmacokinetic-pharmacodynamic modelling of the reversal of buprenorphine-induced respiratory depression by naloxone : a study in healthy volunteers.
Respiratory depression is a potentially life-threatening adverse effect of opioid therapy. It has been postulated that the difficulty of reversing buprenorphine-induced respiratory depression is caused by slow receptor association-dissociation kinetics at the opioid mu receptor. The aim of this study was to characterise the pharmacodynamic interaction between buprenorphine and naloxone in healthy volunteers. ⋯ Because of the slow receptor association-dissociation kinetics of buprenorphine in combination with the fast elimination kinetics of naloxone, naloxone is best administered as a continuous infusion for reversal of buprenorphine-induced respiratory depression.
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The FG loop peptide (FGL(L)), a novel mimetic of the neural cell adhesion molecule (NCAM), is in clinical development for neurodegenerative disorders such as Alzheimer's disease. Preclinical studies in rats, dogs and monkeys have demonstrated exposure in plasma and cerebrospinal fluid after parenteral or intranasal administration of FGL(L), with no systemic toxicity. This article reports on the results of the first administration of FGL(L) in humans. ⋯ Intranasal administration of FGL(L) (25, 100 and 200mg) was well tolerated in healthy male volunteers, with no safety concerns and a pharmacokinetic profile that was generally dose related. Further studies are currently being planned to evaluate the effects of FGL(L) in patients with Alzheimer's disease.
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There is wide variability in the response of individuals to standard doses of drug therapy. This is an important problem in clinical practice, where it can lead to therapeutic failures or adverse drug reactions. Polymorphisms in genes coding for metabolising enzymes and drug transporters can affect drug efficacy and toxicity. ⋯ The studies discussed evaluate different regimens and tumour types and show that polymorphisms can have different, sometimes even contradictory, pharmacokinetic and pharmacodynamic effects in different tumours in response to different drugs. The clinical application of pharmacogenetics in cancer treatment will therefore require more detailed information of the different polymorphisms in drug-metabolising enzymes and drug transporters. Larger studies, in different ethnic populations, and extended with haplotype and linkage disequilibrium analysis, will be necessary for each anti-cancer drug separately.
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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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Treatment of sepsis remains a significant challenge with persisting high mortality and morbidity. Early and appropriate antibacterial therapy remains an important intervention for such patients. To optimise antibacterial therapy, the clinician must possess knowledge of the pharmacokinetic and pharmacodynamic properties of commonly used antibacterials and how these parameters may be affected by the constellation of pathophysiological changes occurring during sepsis. ⋯ In conclusion, certain antibacterials can have a very high V(d), therefore leading to a low C(max) and if a high peak is needed, then this would lead to underdosing. The V(d) of certain antibacterials, namely aminoglycosides and vancomycin, changes over time, which means dosing may need to be altered over time. Some patients with serum creatinine values within the normal range can have very high drug clearances, thereby producing low serum drug levels and again leading to underdosing.