Pharmacokinetics of propofol when given by intravenous infusion.

Abstract

We have previously shown with i.v. bolus studies that the elimination of propofol is much slower than previously reported. Now we have studied the implications of this for prolonged i.v. infusion of propofol in seven patients who received continuous infusions of propofol for up to 9 h. Values of elimination half‐life ranged from 13.1 to 44.7 h, systemic clearance from 1.02 to 1.63 l h‐1 and volume of distribution from 1390 to 3940 l and these were similar to those obtained with bolus administration. The large volume of distribution is consistent with the high octanol/blood partition coefficient, which was found to be 72.0. Despite the very long elimination half‐life, blood propofol concentrations appeared to approach steady state within 20 min rather than the 4‐5 half‐lives normally expected. This is because for this drug, which displays multicompartment pharmacokinetics, the rate of initial rise of blood concentrations is governed primarily by the very short distribution half‐life of the drug. Therefore, the long elimination half‐life of propofol is probably of little significance in designing infusions regimens, but the lower systemic clearance should be taken into account to avoid unwanted accumulation.

Morbid Obesity Alters Both Pharmacokinetics and Pharmacodynamics of Propofol: Dosing Recommendation for Anesthesia Induction

“…Basic pharmacokinetic properties of propofol in humans are well documented (Campbell et al, 1988;Morgan et al, 1990). In line with its highly lipophilic feature, propofol has a very large volume of distribution (Shafer, 1993).…”

“…Although propofol undergoes extensive metabolism (mainly glucuronidation and oxidation) in the liver, it has a very long apparent elimination half-life (Campbell et al, 1988;Favetta et al, 2002). The relatively long elimination is accounted for by the multicompartment pharmacokinetics (PK) of the drug, wherein the elimination process is primarily governed by intercompartment distribution (Morgan et al, 1990). Propofol PK is generally described by a two-compartment (Peeters et al, 2008a;Bienert et al, 2010;Wiczling et al, 2012) or three-compartment (Schnider et al, 1998;van Kralingen et al, 2011) model.…”

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

“…it is also well established that the response to propofol is widely variable among patients receiving the same dose. The drug's binding to serum proteins exceeds 98%, 40 so small changes in protein concentrations can be amplified in the unbound fraction of the drug and in its effect. it is likely that that part of the variability in the response among patients is due to differences in protein levels among individuals and, in particular, among those with pathologies such as liver disease.…”

The “Albumin Effect” and Drug Glucuronidation: Bovine Serum Albumin and Fatty Acid-Free Human Serum Albumin Enhance the Glucuronidation of UDP-Glucuronosyltransferase (UGT) 1A9 Substrates but Not UGT1A1 and UGT1A6 Activities

“…PRO disposition in vivo is well characterized. The mean systemic clearance, generally assumed to be almost entirely due to metabolism, taken from four studies is 108 liters/h (Gepts et al, 1987;Servin et al, 1988;Morgan et al, 1990;Bailie et al, 1992). Glucuronidation accounts for 53% of PRO metabolism in humans (Simons et al, 1988); hence clearance via glucuronidation is 57 liters/h.…”