ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Esmolol is an ultra short-acting intravenous cardioselective &bgr;-antagonist. It has an extremely short elimination half-life (mean: 9 minutes; range: 4 to 16 minutes) and a total body clearance [285 ml/min/kg (17.1 L/h/kg)] approaching 3 times cardiac output and 14 times hepatic blood flow. The &agr;-distribution half-life is approximately 2 minutes. When esmolol is administered as a bolus followed by a continuous infusion, onset of activity occurs within 2 minutes, with 90% of steady-state &bgr;-blockade occurring within 5 minutes. Full recovery from &bgr;-blockade is observed 18 to 30 minutes after terminating the infusion. Esmolol blood concentrations are undetectable 20 to 30 minutes postinfusion. The elimination of esmolol is independent of renal or hepatic function as it is metabolised by red blood cell cytosol esterases to an acid metabolite and methanol. The acid metabolite, which is renally eliminated, has 1500-fold less activity than esmolol. Methanol concentrations remain within the range of normal endogenous levels.Clinically, esmolol is used for the following: (i) situations where a brief duration of adrenergic blockade is required, such as tracheal intubation and stressful surgical stimuli; and (ii) critically ill or unstable patients in whom the dosage of esmolol is easily titrated to response and adverse effects are rapidly managed by termination of the infusion. In adults, bolus doses of 100 to 200mg are effective in attenuating the adrenergic responses associated with tracheal intubation and surgical stimuli. For the control of supraventricular arrhythmias, acute postoperative hypertension and acute ischaemic heart disease, doses of <300 μg/kg/min, administered by continuous intravenous infusion, are used.The principal adverse effect of esmolol is hypotension (incidence of 0 to 50%), which is frequently accompanied with diaphoresis. The incidence of hypotension appears to increase with doses exceeding 150 μg/kg/min and in patients with low baseline blood pressure. Hypotension infrequently requires any intervention other than decreasing the dose or discontinuing the infusion. Symptoms generally resolve within 30 minutes after discontinuing the drug. In surgical and critical care settings where clinical conditions are rapidly changing, the pharmacokinetic profile of esmolol allows the drug to provide rapid pharmacological control and minimises the potential for serious adverse effects.

ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Published values for the serum concentrations and pharmacokinetic parameters of levonorgestrel after administration of various doses of levonorgestrel alone or with ethinylestradiol are reviewed. Most data apply to oral administration of the gestagen, with the smaller amount of data for other modes of administration, e.g. subcutaneous, intravaginal and intra-uterine administration, also included.There is a large variability among the different studies for both serum concentration and pharmacokinetic parameters and not all of this is due to the large interindividual variability demonstrated in all of the studies. The factors responsible for the inter- and intraindividual variability have not been discovered. Sex hormone binding globulin (SHBG) plays an important role in levonorgestrel pharmacokinetics since: (i) levonorgestrel binds strongly to this protein; and (ii) serum SHBG levels are influenced by a large number of different factors including the administration of levonorgestrel and ethinylestradiol. However, not all of the anomalies in the metabolism of levonorgestrel can be ascribed to its interaction with SHBG.

ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

The pharmacokinetics of dipyrone are characterised by rapid hydrolysis to the active moiety 4-methyl-amino-antipyrine (MAA), which has 85% bioavailability after oral administration in tablet form, and takes a short time to achieve maximal systemic concentrations (tmaxof 1.2 to 2.0 hours). Absolute bioavailability after intramuscular and rectal administration is 87 and 54%, respectively. MAA is further metabolised with a mean elimination half-life (t½) of 2.6 to 3.5 hours to 4-formyl-amino-antipyrine (FAA), which is an end-metabolite, and to 4-amino-antipyrine (AA), which is then acetylated to 4-acetyl-amino-antipyrine (AAA) by the polymorphicN-acetyl-transferase (t½of AA is 3.8 hours in rapid acetylators and 5.5 hours in slow acetylators). Urinary excretion of these 4 metabolites accounts for about 60% of the administered dose of dipyrone. Protein binding of the 4 main metabolites is less than 60%. The volume of distribution of MAA is about 1.15 L/kg of lean body mass. All 4 metabolites are excreted into breast milk.A single-dose study (0.75, 1.5 and 3g) and a multiple-dose study (1g 3 times a day for 7 days) revealed nonlinear pharmacokinetics consistent with a shift of MAA metabolism from FAA to AA. Apparent MAA clearance decreased by 22% during multiple administration. MAA clearance was reduced by 33% in the elderly. In patients with cirrhosis of the liver, the apparent clearance of all metabolites is generally reduced. In patients with renal disease, apparent clearance of MAA remains unchanged, whereas elimination of the renally excreted metabolites AAA and FAA is markedly impaired. No clinically important drug interactions have thus far been recognised. Dipyrone does not affect the pharmacodynamic response to alcohol (ethanol), glibenclamide (glyburide), oral anticoagulants or furosemide (frusemide).The low toxicity of dipyrone and its efficacy support its use in clinical practice, despite some complex aspects of its disposition.

ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Drugs administered to mothers have the potential to cross the placenta and reach the fetus. Under particular circumstances, the comparison of the drug concentration in the maternal and fetal plasma may give an idea of the exposure of the fetus to the maternally administered drugs. In this review drugs are classified according to their type of transfer across the placenta.Several drugs rapidly cross the placenta and pharmacologically significant concentrations equilibrate in maternal and fetal plasma. Their transfer is termed ‘complete’. Other drugs cross the placenta incompletely, and their concentrations are lower in the fetal than in maternal plasma. The majority of drugs fit into 1 of these 2 groups. A limited number of drugs reach greater concentrations in fetal than maternal plasma. It is said that these drugs have an ‘exceeding’ transfer. The impression prevails that suxamethonium chloride (succinylcholine chloride) and doxorubicin do not cross the placenta. However, a careful analysis of the literature suggests that this impression is wrong and that all drugs cross the placenta, although the extent transfer varies considerably.The following parameters were considered as possible factors determining the extent of placental transfer: (i) the molecular weight of the drug; (ii) the pKa (pH at which the drug is 50% ionised); and (iii) the extent of drug binding to the plasma protein. Drugs with molecular weights greater than 500D have an incomplete transfer across the human placenta. Strongly dissociated acid drug molecules should have an incomplete transfer, but this does not seem to be an absolute rule. For example, ampicillin and methicillin transfer completely and they are strongly dissociated at physiological pH. The extent of drug binding to plasma protein does not influence the type of drug transfer across the human placenta.

ISSN:0312-5963    

出版商:ADIS    

年代:1995

数据来源: ADIS