Propofol elimination

A report on the binding of the anesthetic propofol to human serum albumin and to plasma presents a dataset that challenges simple notions of equilibria [70]. The unbound fraction of propofol was found to increase sharply at low drug concentrations. The authors appear to have carefully eliminated possible artifacts. Explanations based on cooperative binding modes are discussed though no clear explanation emerges. 

TIVA has become feasible thanks to the introduction of agents with a suitably short duration of action, including the injectable anesthetics propofol and etomidate, the analgesics alfentanil und remifentanil, and the muscle relaxant mivacurium. These drugs are eliminated within minutes after being adminster-ed, irrespective of the duration of anesthesia. 

In that study, propofol had an elimination half-life of 69 min in the horse, with a total body clearance of 33ml/kg/min. The principal site of elimination of propofol is the liver however, the clearance of propofol exceeds hepatic blood flow, suggesting an extrahepatic site of metabolism (Kuipers et al 1999). In dogs, propofol undergoes biotransformation to 4-hydroxypropofol by cytochrome P450 enzymes (Court et al 1999). 

Dawidowicz, A. L., Kalityhski, R., Trocewicz, J., Nestorowicz, A., Pijalkowska, A., Trela-Stachurska, K. (2002). Investigation of propofol renal elimination by HPLC using supported liquid membrane procedure for sample preparation. Biomed. Chromatogr., 16, 455-8. 

Propofol is chiefly eliminated by hepatic conjugation to inactive metabolites, which are excreted by the kidney. A glucuronide conjugate accounts for about 50% of the administered dose. Following an IV bolus dose, plasma levels initially decline rapidly due to both high metabolic clearance and rapid drug distribution into tissues. Distribution accounts for about half of this decline following a bolus of propofol. 

Propofol is metabolized by cytochrome P450 and is glucuronidated. The conjugates are eliminated in the urine. 

Propofol Propofol produces anesthesia at a rate similar to that of the intravenous barbiturates, and recovery is more rapid. Propofol has antiemetic actions, and recovery is not delayed after prolonged infusion. The drug is commonly used as a component of balanced anesthesia and as an anesthetic in outpatient surgery. Propofol may cause marked hypotension during induction of anesthesia, primarily through decreased peripheral resistance. Total body clearance of propofol is greater than hepatic blood flow, suggesting that its elimination includes other mechanisms in addition to metabolism by liver enzymes. 

A further double-blind, placebo-controlled study in 24 patients found that propofol decreased the clearance of midazolam by 37% and increased its elimination half-life by 61%. ... 

IhmsenH, Albrecht S, Fechner J, Bering W, Schuttler J. The elimination of alfentanil is decreased by propofol. 2000 Annual Meeting of the American Society of Anesthesiologists, San... 

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