Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 2009
Risk to the breast-fed neonate from codeine treatment to the mother: a quantitative mechanistic modeling study.
Administering codeine to breast-feeding mothers had been considered safe until the recent death of a breast-fed neonate whose mother had been prescribed codeine. We investigated the risk of opioid poisoning to breast-fed neonates using coupled physiologically based pharmacokinetic models for the mother and child. Neonatal morphine plasma concentrations were simulated for various combinations of cytochrome P450 2D6 (CYP2D6) genotype and morphine clearance, assuming typical breast-feeding schedules and maternal codeine doses of
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Clin. Pharmacol. Ther. · Nov 2009
The impact of continuous renal replacement therapy on drug therapy.
Critically ill patients with multisystem organ failure often require daily administration of large volumes of fluid to provide electrolyte and nutrition support, medications, and blood products. This often results in fluid overload, which has historically been managed with intermittent hemodialysis (IHD). Unfortunately, IHD entails a high rate of fluid and solute removal that often exacerbates hemodynamic instability. Accordingly, continuous renal replacement therapy (CRRT), involving slow and continuous removal of water and solutes from the plasma, is currently preferred for managing these patients.
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Clin. Pharmacol. Ther. · Oct 2009
Imaging and biomarkers in early Alzheimer's disease and mild cognitive impairment.
A major focus of research on aging and dementia pertains to the prediction of future cognitive decline. Toward this end, several longitudinal studies are under way that are designed to explore early predictors of cognitive impairment. Neuroimaging techniques and biomarkers have shown promise in this application. Ultimately, it is likely that the use of a combination of neuroimaging and chemical biomarkers will be involved in predicting the development of dementia and Alzheimer's disease (AD).
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Clin. Pharmacol. Ther. · Oct 2009
Randomized Controlled TrialUse of transdermal melatonin delivery to improve sleep maintenance during daytime.
Oral melatonin (MEL) can improve daytime sleep, but the hormone's short elimination half-life limits its use as a hypnotic in shift workers and individuals with jet lag or other sleep problems. Here we show, in healthy subjects, that transdermal delivery of MEL during the daytime can elevate plasma MEL and reduce waking after sleep onset, by promoting sleep in the latter part of an 8-h sleep opportunity. Transdermal MEL may have advantages over fast-release oral MEL in improving sleep maintenance during adverse circadian phases.