Clin Pharmacokinet
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The administration of osmotic agents is one of the principal strategies to lower elevated intracranial pressure (ICP) and to increase cerebral perfusion pressure. Of the 3 osmotic agents frequently used (mannitol, glycerol and sorbitol), each has characteristic advantages and disadvantages. In addition to renal filtration, sorbitol [elimination half-life (t1/2beta) approximately 1h] and glycerol (t1/2beta 0.2 to 1h) are metabolised, mainly by the liver. ⋯ The ability of mannitol, glycerol and sorbitol to lower elevated ICP has been extensively documented. However, whether the use of osmotic agents, particularly with repeated application, improves outcome remains unproven. Therefore, these agents should only be used to treat manifest elevations of ICP, not for prophylaxis of brain oedema.
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Transdermal delivery allows continuous systemic application of opioids through the intact skin. This review analyses the pharmacokinetic properties of transdermal opioid administration in the context of clinical experience, with a focus on fentanyl. A transdermal therapeutic system (TTS) for fentanyl has been developed. ⋯ Transdermal morphine is only useful if applied to de-epithelialised skin. However, iontophoresis may allow transdermal administration of opioids, including morphine, with a rapid achievement of steady state concentrations and the ability to adjust delivery rates. This would be beneficial for acute and/or breakthrough pain, and initial clinical trials are in progress.