Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1     Pharmacodynamic properties

Pharmacotherapeutic group: Local anaesthetics
ATC code: N01B B01
Bupivacaine Spinal Heavy Panpharma contains bupivacaine, which is a long-acting amide local anaesthetic agent. Bupivacaine reversibly blocks impulse conduction in the nerves by inhibiting the transport of sodium ions through the nerve membrane. Similar effects canalso be seen on excitatory membranes in the brain and cardiac muscle.

Bupivacane Spinal Heavy Panpharma is intended for hyperbaric spinal anaesthesia. The relative density of the solution for injection is 1.026 at 20ºC (equivalent to 1.021 at 37ºC) and the initial distribution in the subarachnoid space is markedly affected by gravity In spinal administration, a small dose is given, which leads to a relatively low concentration and short duration. Bupivacaine spinal (without glucose) produces a less predictable blockade, but with a longer duration compared to Bupivacaine 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 displays complete and biphasic absorption from the subarachnoid space with half-lives for the two phases of approx. 50 and approx. 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 after intravenous administration.

Absorption from the subarachnoid space is relatively slow, which, in combination with the low dose required for spinal anaesthesia, produces relatively low peak plasma concentrations (approx. 0.4 mg/ml per 100 mg injected).

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

Bupivacaine crosses the placenta and the concentration of unbound mepivacaine is the same in the mother and the foetus. However, the total plasma concentration is lower in the foetus, which has a lower degree of protein binding.