Plasma concentration and protein binding of alfentanil during highdose infusion for cardiac surgery

Hynynen, Markku; Hynninen, Marja; Soini, H.; Neuvonen, Pertti J.; Heinonen, Jussi S.

doi:10.1093/bja/72.5.571

Cited by 24 publications

(6 citation statements)

References 16 publications

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“…The most likely explanations for this increase are the dilution of binding protein concentrations (particularly 1 -acid glycoprotein) (20) in plasma by the protein-free priming solution of the CPB apparatus and/or adsorption of proteins on to the CPB equipment (21). Various studies have documented a significant drop in plasma protein levels immediately after CPB connection (22,23). By the end of this study, the unbound fraction of fentanyl had returned to close to its pre-bypass value even though the binding protein concentration may still diminish (22).…”

Section: Discussionmentioning

confidence: 99%

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium

Miller

Peterson

McLean

et al. 1997

Journal of Clinical Pharmacy and Therapeutics

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This study was conducted to examine the effect of cardiopulmonary bypass surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium. Total fentanyl concentrations were measured by gas chromatography, the plasma protein binding of fentanyl by ultrafiltration, and alcuronium concentrations by high-performance liquid chromatography. Sixteen patients were studied. On initiation of cardiopulmonary bypass (CPB), there were mean decreases of 58.8 +/- 7.1% and 47 +/- 3.2% for total concentrations of fentanyl in plasma and haemoglobin in blood, respectively. The magnitude of these reductions in individual patients was significantly related (Spearman p = 0.65, P < 0.05). The unbound fraction of fentanyl rose from 0.23 to 0.34 after the start of CPB. The total fentanyl concentration remained relatively stable during bypass until near the end of CPB when the mean total concentration increased, coinciding with rewarming. The size of the increase was related to the body mass index (BMI) of the patient (Spearman p = 0.85, P < 0.01). The estimated elimination half-life of fentanyl using the grouped data was 4.7 h. The total alcuronium concentration in plasma fell by 29% on initiation of CPB and there was no increase on rewarming. The estimated elimination half-life of alcuronium using the grouped data was 234 min. Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable levels of anaesthesia were maintained throughout the procedure.

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Section: Discussionmentioning

confidence: 99%

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium

Miller

Peterson

McLean

et al. 1997

Journal of Clinical Pharmacy and Therapeutics

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“…A change in plasma binding can result from competitive displacement interactions with other drugs or endogenous substances or reductions in the amount of protein associated with certain disease states such as hepatic or renal failure 3 , 4 , 5 , 6 , 7 , 8 . In addition, certain procedures such as cardiopulmonary bypass (CPB) alter plasma binding 9 , 10 , 11 , 12 , 13…”

mentioning

confidence: 99%

Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding

Hiraoka¹,

Yamamoto²,

Okano³

et al. 2004

Clinical Pharmacology & Therapeutics

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During cardiopulmonary bypass, a significant increase in the concentration of unbound propofol occurred without alteration in the total propofol concentration in blood. The effect of the changes of propofol's protein binding on its kinetics was consistent with the predictions based on the well-stirred model of hepatic elimination for an intravenously infused high-clearance drug. Our finding on propofol pharmacokinetics may be the first example demonstrating the theoretic prediction of the well-stirred model.

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“…Plasma protein binding of drugs may have significant pharmacodynamic implications, because it is the unbound moiety that diffuses most readily across biological membranes, reaches receptor sites to produce pharmacological effects and is available for elimination from the body. Although albumin (ALB) has a greater binding capacity than ␣1-acid glycoprotein (AAG), AAG has much greater drug affinity for drugs with pKa values of 8 or more, and binding of basic drugs decreases in AAG-deficient plasma [1,2]. However, changes in protein binding are only important clinically for drugs which are highly bound to plasma proteins, such as bupivacaine (96 % bound) [3], sufentanil and alfentanil (both 92 % bound) [4].…”

mentioning

confidence: 99%

Perioperative changes in alpha 1-acid glycoprotein concentrations in infants undergoing major surgery

Booker¹,

Taylor²,

Saba³

1996

British Journal of Anaesthesia

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alpha 1-Acid glycoprotein (AAG) is an acute phase protein that is responsible for binding basic drugs such as bupivacaine. In order to determine how AAG concentrations change in response to surgical stress, arterial blood samples were obtained from 50 infants undergoing major surgery, at induction of anaesthesia and daily for the next 7 days. AAG concentrations were measured using a rate nephelometric technique. The overall mean preoperative AAG concentration was 0.38 (SD 0.16) mg ml-1, although concentrations were significantly greater in infants undergoing urgent surgery compared with those undergoing elective surgery (P = 0.02). There were no significant correlations between gestational or postnatal age and preoperative AAG concentration. Mean AAG concentrations increased to 0.76 (0.18) mg ml-1 by day 4 after surgery and stayed at that concentration thereafter. Infants with preoperative AAG concentrations < 0.38 mg ml-1 showed a greater percentage increase in postoperative AAG concentrations than did infants with preoperative AAG concentrations > 0.38 mg ml-1 (P = 0.001). We conclude that preoperative measurement of AAG may identify those infants most at risk of drug toxicity in the early postoperative period.

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Plasma concentration and protein binding of alfentanil during highdose infusion for cardiac surgery

Cited by 24 publications

References 16 publications

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium

Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding

Perioperative changes in alpha 1-acid glycoprotein concentrations in infants undergoing major surgery

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