ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Atracurium is a mixture of 10 isomers. Six of the 10 isomers have been prepared and evaluated for neuromuscular, autonomic and cardiovascular effects in various anaesthetized animal species, including rats, cats, dogs and Rhesus monkeys. All of the isomers exhibited neuromuscular-blocking activity with a 10-fold range of potency, and with the exception of cisatracurium (the purified R-cis, R‘-cisisomer), produced autonomic and cardiovascular effects at doses similar to those of atracurium. Cisatracurium was found to be more potent than atracurium in all of the preclinical studies and, unlike atracurium and all the other isomers, bolus injections of high multiples of the 95% effective neuromuscular-blocking dose did not produce histamine-like cardiovascular effects or increase plasma histamine concentrations. In preclinical studies it was concluded that cisatracurium represents a significant improvement over atracurium.

ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The pharmacokinetics of cisatracurium and its metabolites were evaluated in 56 healthy adult surgical patients with full sampling (17 blood samples collected over 8 h) after single intravenous bolus doses of cisatracurium and in 186 healthy adult surgical patients with sparse sampling (five to eight blood samples collected randomly over 2 h) after single intravenous bolus doses with or without maintenance doses or continuous infusions of cisatracurium. Plasma concentration-time and neuromuscular block data from the patients with full sampling were analyzed using compartmental and non-compartmental pharmacokinetic models and semiparametric effect compartment analyses. Data from all patients were pooled to determine the population pharmacokinetics/pharmacodynamics of cisatracurium. Results fromin vitroandin vivostudies indicated that Hofmann elimination is the predominant pathway for the elimination of cisatracurium in humans. The pharmacokinetics of cisatracurium are independent of the dose from 0.1 to 0.4 mg/kg [two to eight times the dose producing 95% suppression (ED95) of the first evoked twitch response of the adductor pollicis muscle to a train of four stimulations]. Anaesthesia type, sex, estimated creatinine clearance and the presence of obesity were associated with statistically significant effects on the pharmacokinetic/pharmacodynamic parameters for cisatracurium. These covariates were not associated with any clinically significant changes in the predicted recovery profile of cisatracurium. Slight differences in onset were predicted in patients with renal impairment and in patients given inhalation anaesthesia.

ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Cisatracurium is an intermediate-duration, non-depolarizing neuromuscular-blocking agent, the purified form of one of the 10 stereoisomers of atracurium which is cleared primarily by Hofmann elimination. It produces minimal cardiovascular change and does not release histamine even at up to eight times the dose that produced 95% of the maximum response (ED95) for neuromuscular block. At twice the ED95the pharmacodynamic profile of cisatracurium is similar to that of an equipotent dose of atracurium apart from a slightly slower onset of action. A more rapid onset is produced when the dose is increased. The clinically effective duration of action, as assessed by the twitch response of the adductor policis muscle to a train of four stimulations, increases with increasing doses; however, doubling the dose only adds approximately 23 min to the duration of clinically effective block. The clinically effective duration of action ranges from 45 min after twice the ED95(0.1 mg/kg) to approximately 90 min after eight times the Ed95(0.4 mg/kg). Neuromuscular block can be maintained with incremental or repeat bolus doses or continuous infusions of cisatracurium without any cumulative neuromuscular-blocking effect. Neuromuscular block induced with cisatracurium can be readily reversed using anticholinesterase agents. Cisatracurium has a predictable and rapid rate of spontaneous recovery (5–95% recovery about 30 min) irrespective of the initial dose administered or the duration of maintenance dosing.

ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We review four studies, two in Europe and two in the United States, in which the safety and efficacy of cisatracurium for tracheal intubation were determined. The studies were designed to closely reflect normal clinical practice in Europe or the United States. The data indicate that optimal intubation conditions are produced 120 s following a dose of 0.15 mg/kg [three times the dose that produces 95% of the maximum effect (ED95)] cisatracurium or 0.2 mg/kg (four times the ED95) after anaesthesia with propofol or thiopentone. If an anaesthetic induction technique which is typical in the United States is used, including intravenous midazolam (1–2 mg), optimal intubation conditions are produced earlier, at 90 s, following a 0.2 mg/kg dose of cisatracurium.

ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The pharmacodynamics and safety of cisatracurium were determined in children aged 2–12 years. The estimated dose that produced 95% of the maximum effect (ED95) for cisatracurium was 0.04 mg/kg during N2O/O2/halothane anaesthesia. Doses of 0.08 mg/kg (twice the ED95for children during halothane anaesthesia) administered during N2O/O2/halothane anaesthesia and 0.1 mg/kg (twice the Ed95for adults during opioid anaesthesia) administered during N2O/O2/opioid anaesthesia produced maximum suppression of the first evoked electromyographic response by the adductor pollicis muscle to a train of four stimulations (T1) in approximately 2.5 min and provided approximately 30 min of clinically effective block, with full clinical recovery in approximately 45 min. Neuromuscular block was maintained with multiple consecutive doses of cisatracurium without cumulation of the neuromuscular-blocking effect. Administration of cisatracurium at doses up to 0.1 mg/kg (the highest dose studied) was not associated with histamine-mediated cardiovascular effects or cutaneous flushing. Thus cisatracurium can be regarded as a potent, non-cumulative, intermediate-duration neuromuscular-blocking agent which can be used safely and effectively in paediatric patients aged 2–12 years.

ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We performed two studies on the pharmacodynamics and pharmacokinetics of cisatracurium in elderly patients compared with younger adults. The neuromuscular blocking profile and pharmacokinetics of cisatracurium and metabolites were determined following a single 0.1 mg/kg dose of cisatracurium with or without the subsequent administration of an infusion or maintenance doses of cisatracurium. Both studies reported minimal differences in the pharmacokinetics of cisatracurium between elderly patients and younger patients. These minimal differences were associated with a slightly longer time to onset of maximum neuromuscular block in elderly patients than in younger patients but no clinically relevant differences in the recovery profile of cisatracurium. Administration of cisatracurium was not associated with cutaneous flushing or clinically relevant changes in blood pressure or heart rate during the first 5 min following administration to either patient group.

ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Two studies were performed to compare the pharmacodynamics and pharmacokinetics of cisatracurium in healthy control patients and in patients with end-stage renal disease undergoing elective non-transplant surgery or end-stage liver disease undergoing liver transplantation. Minor differences were detected in the pharmacokinetics of cisatracurium in the healthy control patients and in the patients with renal or liver disease. These differences were associated with small changes in the time to onset of neuromuscular blockade, but were not associated with clinicaly relevant differences in the recovery profile of cisatracurium. No adverse effects were observed following the administration of cisatracurium to these patient populations.

ISSN:0952-7907    

出版商:OVID    

年代:1996

数据来源: OVID