Preliminary Pharmacokinetics and Pharmacodynamics of an Ultra-Short-Acting Opioid

Glass, Peter S. A.; Hardman, David; Kamiyama, Yoichiro; Quill, Timothy J.; Marton, Giulia; Donn, Karl H.; Grosse, C M; Hermann, David

doi:10.1213/00000539-199311000-00028

Cited by 536 publications

(315 citation statements)

References 4 publications

(6 reference statements)

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“…The ventilatory response to carbon dioxide has estimated the equilibration half-life to be 2.04 min (À0.24, 4.32 min: 95% confidence intervals) (Babenco et al, 2000). Analgesic measurements have estimated 1.3171.5 min (Glass et al, 1993) These previous estimates by alternative techniques are in agreement with our estimates of t 1/2I ¼ 1.83 min (À2.17, 5.83 min: 95% confidence intervals) from the insular cortical BOLD response and t 1/2I ¼ 2.80 min (À0.12, 5.73 min: 95% confidence intervals) for reported pain intensity.…”

Section: Discussionmentioning

confidence: 99%

“…The time dependence of drug action may be measured from the effects of the drug on the body, known as the pharmacodynamics. In the case of remifentanil, pain threshold (Glass et al, 1993) has been used to characterize the time dependence of the analgesic effect. Additionally, less analgesia-relevant measures have been employed including spectral characteristics of the electroencephalogram (Egan et al, 1996;Hermann et al, 1999;Hoke et al, 1997;Minto et al, 1997a, b), which provides a measure of brain activity, but is not spatially localized, requires doses beyond the normal clinical range and more importantly is not directly associated with pain processing.…”

Section: Introductionmentioning

confidence: 99%

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Using fMRI to Quantify the Time Dependence of Remifentanil Analgesia in the Human Brain

Wise

Williams

Tracey

2003

Neuropsychopharmacol

108

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To understand and exploit centrally acting drugs requires reliable measures of their time course of action in the human brain. Functional magnetic resonance imaging (fMRI) is able to measure noninvasively, drug-induced changes in task-related brain activity. Here, we have characterized, in a specific region of the brain, the time of onset of action and the half-life of action of a clinically relevant dose of a potent opioid analgesic agent, remifentanil. These times were established from the temporal variation of the amplitude of the blood oxygen level-dependent response in the insular cortex contralateral to a painfully hot thermal stimulus, in volunteers receiving a remifentanil infusion. The insular cortex has repeatedly been reported as activated by noxious thermal stimulation. The times of onset and offset of drug action were each characterized by a half-life for changes in fMRI signal from within the insula. These characteristic times agreed with the observed drug-induced analgesia and previous pharmacokinetic-pharmacodynamic measurements for remifentanil. We have successfully measured, for the first time using fMRI, temporal pharmacological parameters for a CNS-active drug based on its effect on task-related activity in a specific brain region. Comparison of the time course of regional brain activity with pain perception could reveal those regions engaged in drug-induced analgesia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Using fMRI to Quantify the Time Dependence of Remifentanil Analgesia in the Human Brain

Wise

Williams

Tracey

2003

Neuropsychopharmacol

108

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“…In the circulation, remifentanil is rapidly hydrolysed by plasma and tissue esterases (tu213 = 12-25 min), producing several inactive metabolites. 4 Of equal importance from a kinetic perspective, the drug has a small volume of distribution. It is the combination of these two properties which characterizes remifentanil as a truly ultra-short acting opioid analgesic, and offers the potential for re-exploring the manner in which opioid actions are titrated to clinical effect in the perioperafive setting.…”

Section: New Drugsmentioning

confidence: 99%

Intravenous anaesthesia: new drugs, new concepts, and clinical applications

Miller

1996

Can J Anaesth

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During the course of the past decade, three distinct developments have resulted in the widespread clinical application of intravenous anaesthesia: (a) the world-wide introduction of propofol and alfentanil in the late 1980s; (b) enhanced understanding of the pharmacodynamics and pharmacokinetics of iv anaesthetic drugs (e.g., context-sensitive half-times); (c) commercial availability of programmable ,syringe infusion pumps for intravenous infusion techniques While many of the advantages and some of the limitations of iv anaesthesia are now well-apparent, further refinement and establishment of techniques employing predominantly iv anaesthetic drugs are focusing upon several important areas. These include continued development of new, short-acting drugs which have minimal side-effects and increasingly predictable durations of action; quantitation of drug interactions; research in the area of drug delivery systems; and pharmacoeconomic evaluation of iv anaesthetic techniques. While the last two issues constitute entities unto themselves, this Refresher Course Lecture will focus primarily on new iv drugs, new methods to predict recovery from iv anaesthesia, drug interactions, and practical applications of these principles. Objectives(i) To review how the characteristics of an "ideal" iv anaesthetic drug apply to the new opioid analgesic, remifentanil. (ii) To predict the potential clinical applications of an ultra-short acting opioid analgesic. (iii) To compare and contrast three predictors of recovery from iv anaesthetics: relevant effect-site decrement time, context-sensitive half-time, and mean effect time. (iv) To review basic principles of drug interaction, and to apply these to benzodiazepine/propofol, and propofol/opioid combinations. (v) To establish optimal infusion regimens for iv anaesthetic drugs. (vi) To review practical applications and techniques for obtaining maximum benefit from iv infusion anaesthesia. New drugsPropofol has been available in Canada for more than five years, and while many of its desirable attributes and limitations are now well-defined, t studies related to pharmacological interactions, and cost-effectiveness of this drug are ongoing. However, propofol, which has provided a major advance in clinical anaesthesia, can no longer be considered "new," and the search continues for even better sedative-hypnotics and opioid analgesics. The characteristics desirable of an "ideal" iv anaesthetic drug are listed in Table I. While many of these characteristics may appear obvious, they highlight the necessary attributes for drug development in the cost-conscious 1990s.For new drugs to be incorporated into clinical practice, they must have unique pharmacokinetic and pharmacodynamic properties, a high therapeutic index and favourable side effect profile, while at the same time providing either a comparable, or improved cost-benefit compared with existing drugs of the same class. 2.3In the area of sedative-hypnotics, eltanolone is being evaluated in Europe, although it appears that this drug lack...

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“…Remifentanil is a new, ultra-short acting, selective mureceptor agonist that is 20-30 times more potent than alfentanil [1]. It is the hydrochloride salt of 3-[4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidine] propanoic acid, methyl ester [2].…”

mentioning

confidence: 99%

“…It is the hydrochloride salt of 3-[4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidine] propanoic acid, methyl ester [2]. Its ester linkage renders it susceptible to hydrolysis by blood and tissue nonspecific esterases [3] resulting in a short terminal half-time of < 10 min at the site of action [1]. Remifentanil has a context-sensitive half-time of 3.65 min [4] compared with alfentanil with 58.5 min after a 4-h infusion [5].…”

mentioning

confidence: 99%

Comparison of remifentanil with alfentanil or suxamethonium following propofol anaesthesia for tracheal intubation

et al. 1999

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SummarySixty ASA physical status I and II, premedicated patients were administered propofol 2 mg.kg ¹1 and remifentanil 2 mg.kg ¹1 (group R), alfentanil 50 mg.kg ¹1 (group A) or suxamethonium 1 mg.kg ¹1 (group S) as a rapid bolus. One minute after study drug administration, tracheal intubation was performed. Intubation conditions were then scored. Excellent or good conditions were observed in only 35% in group R compared with groups S and A (100% and 85%, respectively; p < 0.001). The haemodynamic response to tracheal intubation was blunted in groups R and A compared with group S (p < 0.001). The mean heart rate in groups R and A was significantly lower than group S (p < 0.001). We conclude that remifentanil 2 mg.kg ¹1 given as a rapid bolus will not produce intubating conditions as good as those obtained with alfentanil 50 mg.kg ¹1 or suxamethonium 1 mg.kg ¹1 if administered after propofol 2 mg.kg ¹1 .

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Preliminary Pharmacokinetics and Pharmacodynamics of an Ultra-Short-Acting Opioid

Cited by 536 publications

References 4 publications

Using fMRI to Quantify the Time Dependence of Remifentanil Analgesia in the Human Brain

Using fMRI to Quantify the Time Dependence of Remifentanil Analgesia in the Human Brain

Intravenous anaesthesia: new drugs, new concepts, and clinical applications

Comparison of remifentanil with alfentanil or suxamethonium following propofol anaesthesia for tracheal intubation

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