Binding of Anilide-type Local Anesthetics in Human Plasma

Tucker, Geoffrey T.; Boyes, R. N.; Bridenbough, Phillip O.; Moore, Daniel C.

doi:10.1097/00000542-197009000-00006

Cited by 67 publications

(5 citation statements)

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“…Our present data suggest that, in contrast to other amide type local anaesthetics (1 7), there is no change in protein binding when total concentrations of the drug vary over a clinically important range up to 16 pg/ml. These experimental data of unaffected protein binding even at high plasma concentrations correspond well with the results of Tucker et al (18), who proposed that prilocaine is the drug of choice in intravenous anaesthesia, when large amounts of local anaesthetic drugs are necessary. At the moment of cuff release following intravenous anaesthesia of the upper extremity, a sudden rise in plasma concentration of more than 10 pg/ ml must be expected (19).…”

Section: Discussionsupporting

confidence: 89%

Protein binding of prilocaine in human plasma: influence of concentration, pH and temperature

Bachmann

Biscoping

Sinning

et al. 1990

Acta Anaesthesiol Scand

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Protein binding of prilocaine was investigated in vitro under various conditions of changing pH, temperature and total plasma concentration by means of HPLC with UV-detection and ultrafiltration. Whereas changes in temperature (25"G4OoC) and pH (pH 5-pH 10) influenced protein binding markedly, rising plasma concentrations up to 16 pg/ml did not affect plasma protein binding significantly. This may be a possible explanation for clinical evidence of low toxicity associated with the use of prilocaine. Discussions concerning protein binding of local anaesthetics should always be based on defined ambient conditions (pH, temperature, concentration).

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Section: Discussionsupporting

confidence: 89%

Protein binding of prilocaine in human plasma: influence of concentration, pH and temperature

Bachmann

Biscoping

Sinning

et al. 1990

Acta Anaesthesiol Scand

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“…The marked difference between the mean peak plasma level of etidocaine (1.51 pg/ml) and the mean peak whole blood level (0.82 pg/ml) indicates that 91 yo of etidocaine is bound to plasma proteins and only 9% is free to diffuse across the red blood cell membrane. This figure of approximately 90% plasma protein binding for etidocaine agrees well with figures previously presented by ROYES (1974) and with protein binding values reported for bupivacaine (TUCKER et al 1970).…”

Section: Side Efkts Blood Levels and Plasma Protein Bindingsupporting

confidence: 92%

A Comparison of the Local Anesthetic Properties of Bupivacaine and Two New Long‐Acting Agents, HS 37 and Etidocaine, in Epidural Analgesia

Engberg¹,

Holmdahl²,

Edström³

1974

Acta Anaesthesiol Scand

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Two new local anesthetics, HS 37 and etidocaine, were evaluated in epidural analgesia and compared with bupivacaine. Initially, a dose-response study was conducted in which concentrations of etidocaine of 0.75%, 1% and 1.5% and concentrations of HS 37 of 0.75% and 1% were employed.On the basis of this study, a double-blind study was performed with 1% etidocaine, 1% HS 37 and 0.5% bupivacaine. This latter study indicated no difference in onset time and duration of maximal segmental spread. Bupivacaine possessed a significantly longer total duration of sensory analgesia. The frequency of satisfactory surgical anesthesia and segmental spread of analgesia were similar for etidocaine and bupivacaine. The frequency of anesthetic supplementation was greater for HS 37 due to a more restricted spread of segmental anesthesia in the sacral area. Etidocaine showed a significantly greater depth of motor paralysis than either bupivacaine or HS 37.Side effects or methemoglobinemia were not observed with any of the agents. Venous blood concentrations of etidocaine following the use of 300 mg revealed a peak plasma level of 1.51 pg/ml and a whole blood concentration of 0.82 pg/ml. The results showed HS 37 and etidocaine to be long-acting local anesthetics comparable to bupivacaine.

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“…Alternatively, the observed effects may reflect a pharmacokinetic interaction. Bupivacaine demonstrates concentration-dependent protein binding [26], with free bupivacaine concentrations increasing from 5% of total plasma concentration in the 1^1 mg litre" 1 range to 50% at concentrations of 12 mg litre" 1 . In addition, diltiazem is subject to displacement in vitro by bupivacaine [27].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Bupivacaine Toxicity by Diltiazem in Anaesthetized Dogs †

Finegan

Whiting

Tam

et al. 1992

British Journal of Anaesthesia

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We have studied the cardiovascular effects of graded doses of bupivacaine in the absence or presence of clinical concentrations (approximately 250 micrograms litre-1) of diltiazem in fentanyl-pentobarbitone anaesthetized dogs. Bupivacaine was given, increasing in a stepwise manner, as a loading dose (200, 400 or 600 micrograms kg-1) followed by a 30-min i.v. infusion (25, 100 or 200 micrograms kg-1 min-1, respectively). Thereafter, bupivacaine was infused at 400 micrograms kg-1 min-1 until each animal died. Group A (n = 7) received bupivacaine, group B (n = 5) diltiazem (400 micrograms kg-1 followed by 12 micrograms kg-1 min-1) and group C (n = 7) received diltiazem followed by bupivacaine given as in group A. Lethal plasma concentrations of bupivacaine were significantly smaller (P < 0.01) in group C (7.1 (SEM 0.7) vs 12.6 (1.5) mg litre-1). Bupivacaine produced similar decreases in cardiac index, left ventricular (LV) segmental work and the first derivative of LV pressure (LV dP/dt) in the absence and presence of diltiazem. In group A, bupivacaine increased systemic vascular resistance index (SVRI) and thus mean arterial pressure (MAP) was maintained. In group C, SVRI, reduced by diltiazem per se, did not increase in response to bupivacaine, so MAP was not maintained. Death resulted from a progressive decrease in cardiac contractility and MAP. Plasma concentrations of bupivacaine attained at the three doses were similar in the absence and presence of diltiazem. This study has shown that the toxicity of bupivacaine was increased approximately two-fold by diltiazem.

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Binding of Anilide-type Local Anesthetics in Human Plasma

Cited by 67 publications

References 0 publications

Protein binding of prilocaine in human plasma: influence of concentration, pH and temperature

Protein binding of prilocaine in human plasma: influence of concentration, pH and temperature

A Comparison of the Local Anesthetic Properties of Bupivacaine and Two New Long‐Acting Agents, HS 37 and Etidocaine, in Epidural Analgesia

Enhancement of Bupivacaine Toxicity by Diltiazem in Anaesthetized Dogs †

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