부산대학교 도서관

Knowledge of the factors influencing the plasma drug concentration–time profiles (pharmacokinetics) of local anaesthetics (Figure 7.1) underpins their safe and effective use. The plasma drug concentration provides information not only on the margin of systemic safety, but also, indirectly, on the amount of dose yet to be absorbed and still available locally for anaesthetic effect. The relevant pharmacokinetic properties are determined by the physicochemical and structural features of the compounds. The former, in particular lipid solubility, have a major influence on systemic absorption rate and hence duration of activity. In concert with chemical structure, they determine how and at what rate the compound is removed from the body. In addition, stereochemical features (Chapter 6) can also modulate pharmacokinetic properties. The key physicochemical properties of the main local anaesthetics are shown in Table 6.1. Of the amides, only lidocaine is achiral, the rest have an asymmetric carbon atom, giving rise to the possibility of two stereoisomers. Prilocaine and mepivacaine are available as racemates (50:50 mixtures of the two isomers), ropivacaine as the single S-isomer, and bupivacaine as either the racemate or the single S-isomer (levobupivacaine). Consideration of the pharmacokinetics of local anaesthetic agents can be divided into three aspects: local disposition, systemic absorption, and systemic disposition.