Anomalous relationship between free drug fraction and its total concentration in drug–protein systems

Dawidowicz, Andrzej L.; Kobielski, Mateusz; Pieniadz, Jaroslaw

doi:10.1016/j.ejps.2008.02.004

Cited by 18 publications

(2 citation statements)

References 18 publications

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“…Therefore, the higher concentration of unbound propofol could explain the significantly lower BIS values observed in CPB-H patients after TCI cessation (i.e., greater effect) compared with those found in OPCAB patients. These observations are consistent with those previously reported in the literature 4 - 6 , 9 , 15 , 16 .…”

Section: Discussionsupporting

confidence: 94%

Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass

Silva-Filho¹,

Barbosa²,

Silva-Jr³

et al. 2018

Clinics

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OBJECTIVES:The objective of this study was to apply a pharmacokinetics-pharmacodynamics approach to investigate the free propofol plasma levels in patients undergoing coronary artery bypass grafting under hypothermic conditions compared with the off-pump procedure.METHODS:Nineteen patients scheduled for on-pump coronary artery bypass grafting under hypothermic conditions (n=10) or the equivalent off-pump surgery (n=9) were anesthetized with sufentanil and propofol target-controlled infusion (2 μg/mL) during surgery. The propofol concentration was then reduced to 1 μg/mL, and a pharmacokinetics-pharmacodynamics analysis using the maximum-effect-sigmoid model obtained by plotting the bispectral index values against the free propofol plasma levels was performed.RESULTS:Significant increases (two- to five-fold) in the free propofol plasma levels were observed in the patients subjected to coronary artery bypass grafting under hypothermic conditions. The pharmacokinetics of propofol varied according to the free drug levels in the hypothermic on-pump group versus the off-pump group. After hypothermic coronary artery bypass was initiated, the distribution volume increased, and the distribution half-life was prolonged. Propofol target-controlled infusion was discontinued when orotracheal extubation was indicated, and the time to patient extubation was significantly higher in the hypothermic on-pump group than in the off-pump group (459 versus 273 min, p=0.0048).CONCLUSIONS:The orotracheal intubation time was significantly longer in the hypothermic on-pump group than in the off-pump group. Additionally, residual hypnosis was identified through the pharmacokinetics-pharmacodynamics approach based on decreases in drug plasma protein binding in the hypothermic on-pump group, which could explain the increased hypnosis observed with this drug in this group of patients.

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Section: Discussionsupporting

confidence: 94%

Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass

Silva-Filho¹,

Barbosa²,

Silva-Jr³

et al. 2018

Clinics

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show abstract

“…The effects of propofol occur in the plasma by its free form. Free fraction of propofol can be increased by various drugs that could bind to the same site on albumin, conformational alterations of molecular albumin or changes in plasma protein concentration change free propofol dose in plasma (Dawidowicz et al, 2008). The plasma concentration of propofol should be between 5-50 μmol/L.…”

Section: Introductionmentioning

confidence: 99%

Affinity of Propofol to Human Serum Albumin and Cardiovascular Effects

Özaltun

Selamoğlu

2019

Turkish JAF Sci.Tech.

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Propofol is used in general anesthesia and sedation. İt is an lipofilic agent and metabolize to inactive form in liver then excreted in the urine. In body it is turnover changes by human serum albumin amount. >97% of propofol is bound to serum albumin. So that hypoalbunemia changes propofol effects. Free form of propopol can pass all membrans such as the blood-brain barrier and the cellular membrane of the cardiac endothelium. Propofol may cause significant myocardial depression, decrease blood pressure and cause life threatining arytmias. Changes in the ratio of free and bound forms of propofol and albumin depending on the dose and duration of administration, the effects of this ratio on cardiac profile are discussed in this study. According to the findings, it was determined that the albumin affinity of propofol decreased in all dose groups in time. Since free HSA and free propofol ratio will increase, this situation is thought to affect the cardiac profile negatively.

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Protein Binding and Drug Distribution

Zheng,

Musteata

2023

Oral Bioavailability and Drug Delivery

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Anomalous relationship between free drug fraction and its total concentration in drug–protein systems

Cited by 18 publications

References 18 publications

Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass

Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass

Affinity of Propofol to Human Serum Albumin and Cardiovascular Effects

Protein Binding and Drug Distribution

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