English

THIOPENTAL PHARMACOKINETICS

Thiopental pharmacokinetic parameters
Clearance (CL) 10 L/h
Volume of distribution (Vd) 160 L
Elimination half-life (t1/2) 10 h
Distribution half-life (t1/2) 1 h

Description

Thiopental is used in the induction of anesthesia and for the control of convulsive states. It is a short acting barbiturate with sedative, hypnotic and anticonvulsant properties. The brain sensitivity to thiopental shows interindividual variability. Therefore, the dosage of thiopental needed during surgery shows considerable individual variations.

Thiopental is usually used as an intravenous injection. Therefore, absorption is complete and instantaneous.

Thiopental is non polar, lipophilic and only partially ionized at plasma pH. As such, its entry into both brain and muscle occurs readily and is perfusion rate limited. Therefore, thiopental equilibrates rapidly in highly perfused organs, like the nervous system and viscera, while its distribution into less perfused organs like muscle and adipose tissue is considerably delayed. After bolus injection, termination of the drug effect mainly results from redistribution from its site of action (the highly perfused brain) into other tissues (e.g. the poorly perfused adipose tissue). Fat is a reservoir for thiopental and the intensity of fat uptake accounts for between two-thirds and tree-quarters of the administered dose. In the plasma, thiopental is bound predominantly to albumin (75-90%). Thiopental crosses the placenta easily.

Acute thiopental action is limited by redistribution and not by metabolic breakdown. The role of metabolism becomes more relevant after repeated administration of high doses of thiopental in neurotraumatology. Thiopental is almost completely biotransformed in the liver to mostly inactive metabolites, which are then excreted in the urine. A very small percentage of the dose is excreted unchanged in the urine. Metabolic autoinduction can occur when patients are treated with high doses of thiopental over a prolonged period in the intensive care unit.

Clinical implications

For induction of anesthesia, the rapid redistribution of thiopentoui mal accounts for the short duration of effect, while during prolonged administration, the elimination half-life of the drug accounts for the longer lasting effect. Anesthetists call this effect the context dependant half-life.

Lower thiopental requirements have been reported in the elderly. The lean body mass (LMB) decreases with increasing age. Cardiac output also decreases with increasing age and is an important determinant of initial intravascular drug mixing and therefore affects the dose of a drug with rapid onset of effect, such as thiopental when administered by bolus. The dosage of thiopental must also be adapted in patients with liver damage and patients with heart failure.

Obesity influences the thiopental induction dose; the dose was significantly less per kg in obese patients, because the initial volume of distribution is similar between obese and lean patients, before redistribution occurs. However, for long term administration of thiopental to treat seizures, the volume of distribution at steady-state is 3 to 4 times higher in obese compared with lean patients, probably due to the extreme lipophily of thiopental. Because of this larger volume of distribution, the elimination half-life of thiopental is prolonged in obese patients.