Abstract
Aim:
It is generally assumed that only unbound drugs can reach the site of action by diffusing across the membranes and exerting pharmacological effects by interacting with receptors. Recent research has shown that the percentage of free drugs may depend on the total drug concentration. The aim of the paper is to verify whether the mentioned dependence reported for propofol also takes place in plasma and human serum albumin samples in the presence of intralipid — the medium used as a vehicle for propofol infusions and a parenteral nutrition agent.
Methods:
Artificial plasma samples and human plasma were spiked with intralipid or ethanolic solutions of propofol. The samples were then assayed for free propofol concentration using ultrafiltration and high performance liquid chromatography with fluorimetric detection.
Results:
The decrease of the total drug concentration results in free propofol fraction increase, irrespectively of the used type of propofol solvent and sample type. The addition of intralipid causes the lowering of the overall free drug fraction with respect to the samples spiked with ethanolic solutions of the drug.
Conclusion:
The presence of intralipid does not influence the phenomenon of free propofol fraction rise at low total drug concentration. Such a rise cannot be ignored in clinical conditions when the drug is applied for sedative, antiemetic or other low-dosage purposes.
Similar content being viewed by others
Article PDF
References
Mehta AC . Therapeutic monitoring of free (unbound) drug levels: analytical aspects. Trends Anal Chem 1989; 8: 107–12.
Paxton JW . Drug binding to plasma proteins. N Z Med J 1985; 98: 245–8.
Svensson CK, Woodruff MN, Baxter JG, Lalka D . Free drug concentration monitoring in clinical practice, rationale and current status. Clin Pharm 1986; 11: 450–69.
Olsen GD, Bennett WM, Porter GA . Morphine and phenytoin binding to plasma proteins in renal and hepatic failure. Clin Pharmacol Ther 1975; 17: 677–84.
Gin T . Pharmacodynamics of propofol and free drug concentrations. Anesthesiology 1993; 78: 604.
Vuyk J, Engbers FH, Lemmens HJ, Burm AG, Vletter AA, Gladines MP, et al. Pharmacodynamics of propofol in female patients. Anesthesiology 1992; 77: 3–9.
Dawidowicz AL, Kalitynski R . HPLC investigation of free and bound propofol in human plasma and cerebrospinal fluid. Biomed Chromatogr 2003; 17: 447–52.
Dawidowicz AL, Kalitynski R, Fijalkowska A . Relationships between total and unbound propofol in plasma and CSF during continuous drug infusion. Clin Neuropharmacol 2004; 27: 129–32.
Dawidowicz AL, Kalitynski R . Effects of intraoperative fluid infusions, sample storage time, and sample handling on unbound propofol assay in human blood plasma. J Pharm Biomed Anal 2005; 37: 1167–71.
Borgeat A, Wilder-Smith OH, Suter PM . The nonhypnotic therapeutic applications of propofol. Anesthesiology 1994; 80: 642–56.
Dawidowicz AL, Kalitynski R, Kobielski M, Pieniadz J . Influence of propofol concentration in human plasma on free fraction of the drug. Chem Biol Interact 2006; 159: 149–55.
Zamacona MK, Suarez E, Garcia E, Aguirre C, Calvo R . The significance of lipoproteins in serum binding variations of propofol. Anesth Analg 1998; 87: 1147–51.
Plummer GF . Improved method for the determination of propofol in blood by high-performance liquid chromatography with fluorescence detection. J Chromatogr 1987; 421: 171–6.
Takizawa E, Hiraoka H, Takizawa D, Goto F . Changes in the effect of propofol in response to altered plasma protein binding during normothermic cardiopulmonary bypass. Br J Anaesth 2006; 96: 179–85.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kalitynski, R., Dawidowicz, A. & Poszytek, J. Influence of intralipid on free propofol fraction assayed in human serum albumin solutions and human plasma. Acta Pharmacol Sin 27, 1637–1641 (2006). https://doi.org/10.1111/j.1745-7254.2006.00454.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2006.00454.x