Evaluation of clinical tolerance of local anaesthetic agents

The clinical tolerance to local anaesthetic drugs can be assessed from a knowledge of their pharmacokinetic behaviour, their absorption properties and the effects produced by controlled i.v. infusions. Pharmacokinetic behavior can be calculated from the plasma concentrations of the drugs injected i.v. in non-toxic doses. Absorption properties can likewise be determined from plasma concentrations following injection at various sites. Acute toxicity can be assessed by i.v. infusion of toxic doses into volunteers. The dosage required to produce symptoms can be compared with other drugs. Such dosage is considerably affected by the rate of injection. The venous plasma concentrations at the height of toxicity are unreliable guides to toxicity. Experiences using the new local anaesthetic etidocaine are reported.