The binding of local anaesthetics by plasma proteins influences the duration of action. The amide local anaesthetics are mainly bound to α1-glycoproteins. This can affect the pharmacokinetics and dynamics of a drug. Typical plasma protein binding values of the local anaesthetics are as follows:

• Bupivacaine 95%
• Ropivacaine 94%
• Levobupivacaine 97%
• Lidocaine 75%

Lipid solubility appears to be the most significant property of local anaesthetic molecules in determining anaesthetic potency. The lipid nature of the nerve cell membrane probably explains this relationship between lipid solubility and potency. Local anaesthetic molecules that are highly lipophilic easily penetrate nerve cell membranes.

Tissue pKa and relationship to pH will determine the degree of ionisation. The pKa of a local anaesthetic will determine the speed of onset. Un-ionised molecules readily penetrate nerve cell membranes and at a pH of 7.4 the onset of lidocaine is quicker than bupivacaine.

• Lidocaine (pKa 7.7) approximately 33% exists in the un-ionised form
• Bupivacaine (pKa 8.1) approximately 17% exists in the un-ionised form.

Amide local anaesthetics are metabolised in the liver and are not subject to local metabolism.