Clin Pharmacokinet
-
Review
Pharmacokinetic optimization of benzodiazepine therapy for acute seizures. Focus on delivery routes.
All benzodiazepines enter cerebral tissue rapidly. However, the duration of action is short for diazepam (< 2 hours) and midazolam (3 to 4 hours) and longer for clonazepam (24 hours) and lorazepam (up to 72 hours), and is not correlated with the plasma concentration-time profiles of these drugs. Although a relationship between the plasma concentration of diazepam, lorazepam and midazolam and their pharmacodynamic effect has been demonstrated in healthy individuals, some caution is warranted as the clinical relevance of these data has not been clearly established. ⋯ According to the route of administration, the efficacy was 28.6 to 100% (intrarectal) and 54 to 100% (intravenous) for diazepam, 82 to 100% (intravenous) for lorazepam, and 79% (intranasal), 93 to 100% (intramuscular) and 100% (intravenous) for midazolam. Although diazepam was initially chosen for the management of refractory status epilepticus, the longer duration of action of lorazepam and clonazepam may favour the use of these 2 drugs. However, double-blind evaluations are necessary to determine which drug is best.
-
The pharmacokinetics of 6 new neuromuscular blocking drugs are described. These are the aminosteroids pipecuronium bromide, rocuronium bromide and rapacuronium bromide (ORG-9487) and the benzylisoquinolinium diesters doxacurium chloride, mivacurium chloride and cisatracurium besilate. In healthy individuals, these drugs all have similar volumes of distribution. ⋯ It is mainly broken down by Hofmann (non-enzymatic) degradation. Cisatracurium has an intermediate clearance (0.3 L/h/kg) and short elimination half-life (26 minutes). Hepatic and renal disease have little effect on its pharmacokinetics.
-
Randomized Controlled Trial Clinical Trial
Interaction potential and tolerability of the coadministration of cilostazol and aspirin.
This study evaluated the effects of repeated oral drug administration with cilostazol alone and with aspirin (acetylsalicylic acid) on platelet aggregation, coagulation and bleeding time as well as the cilostazol-aspirin pharmacokinetic interaction in healthy males. ⋯ Cilostazol and aspirin coadministration did not cause clinically significant changes in PT, aPTT, bleeding time, platelet aggregation or plasma concentrations of cilostazol and its 2 active metabolites. Cilostazol was generally well tolerated with or without aspirin.
-
Sevoflurane is a comparatively recent addition to the range of inhalational anaesthetics which has been recently released for clinical use. In comparison to older inhalational agents such as isoflurane or halothane, the most important property of sevoflurane is its low solubility in the blood. This results in a more rapid uptake and induction than the 'older' inhalational agents, improved control of depth of anaesthesia and faster elimination and recovery. ⋯ The hepatic metabolism of sevoflurane results in the formation of inorganic fluoride. Upon contact with alkaline CO2 absorbent, a small amount of sevoflurane is degraded and a metabolite (compound A) is formed and inhaled in trace amounts. Whether inorganic fluoride or compound A are nephrotoxic is presently a matter of controversy.
-
There are considerable laboratory data and information from animal and continuous culture in vitro models to support continuous infusion therapy for penicillins and cephalosporins, but, as yet, the only existing clinical data relate to cephalosporins. Penicillins do not exert concentration-dependent killing in the therapeutic range but have a post-antibiotic effect (PAE) against Gram-positive cocci but not Gram-negative rods. Animal models indicate the time (T) during which the serum concentrations exceed the minimum inhibitory concentration (MIC) of the pathogen [T > MIC] determines outcomes. ⋯ As an approximation, the same total daily dose should be given but a bolus intravenous injection should be give at the start of continuous infusion to ensure Css is reached rapidly. The Css may be difficult to predict and determination of serum drug concentrations may be indicated. Ideally, the Css should be calculated based on the MIC of the potential pathogen and may be higher or lower than the Css achieved by a conventional daily dose.