Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1      Pharmacodynamic properties
Pharmacotherapeutic group: Local anaesthetics
ATC code: N01B B01

Marcaine Spinal contains bupivacaine, which is a long-acting amide-type local anaesthetic.
Bupivacaine reversibly blocks impulse transmission in nerves by inhibiting the transport of sodium ions over the nerve cell membrane. Similar effects can also be seen on excitatory membranes in the brain and cardiac muscle.

Marcaine Spinal is intended for spinal anaesthesia. The relative density of the solution for injection is 1.004 at 20ºC (equivalent to 1.000 at 37ºC) and the distribution is only marginally affected by gravity.

When administered to the spine, a small dose is given; this leads to a relatively low concentration and a short duration of action. Marcaine Spinal (without glucose) results in a less predictable blockade but has a longer duration compared with Marcaine Spinal Heavy (with glucose).

Pharmacokinetic Properties

5.2      Pharmacokinetic properties
Bupivacaine is highly lipid soluble with an oil/water distribution coefficient of 27.5.
Bupivacaine demonstrates total and biphasic absorption from the subarachnoid space.
T h e half-lives of the two phases are approx. 50 and 400 minutes, with large variations. The slow absorption phase is a rate-determining factor in the elimination of bupivacaine, which explains why the apparent half-life is longer than that following intravenous administration.
Absorption from the subarachnoid space is relatively slow, which, in combination with the low dose required for spinal anaesthesia gives, a relatively low maximal plasma concentration (approx. 0.4 mg/ml per injected 100 mg).

Following intravenous administration, the total plasma clearance is approx. 0.58 l/min, the volume of distribution at steady state is 73 l, the elimination half-life is 2.7 hours, and the hepatic extraction ratio is approx. 0.40. Bupivacaine is almost entirely metabolised in the liver, particularly through aromatic hydroxylation to 4-hydroxy-bupivacaine and N- dealkylation to PPX, both of which are mediated by cytochrome P450 3A4. Clearance is therefore dependent on the hepatic blood flow and the activity of the metabolising enzyme.

Bupivacaine crosses the placenta and the concentration of unbound mepivacaine i n the mother and foetus is equalised. However, the total plasma concentration will be lower in the foetus, due to a lower degree of protein binding.