The partition coefficient as a predictor of local anesthetic potency for spinal anesthesia: evaluation of five local anesthetics in a mouse model.
Local anesthetic partition coefficients correlate with drug potencies in vitro, but in vivo data have not always complimented in vitro results. Despite extensive studies on intrathecal anesthetic action, whether there is correlation between the partition coefficient and local anesthetic potency has not been addressed. Mice (n = 150) were randomly allocated into 15 groups. Intrathecal injections of etidocaine (E), tetracaine (T), bupivacaine (B), lidocaine (L), or procaine (P) were administered and analgetic effect was measured using tail-flick (TF) test. Concentration-response regressions were constructed for each drug; EC50 values were calculated and compared at 95% confidence intervals. The EC50 values between E (0.017%), T (0.019%), and B (0.012%) were not significantly variant. The EC50 of L (0.098%) and P (0.229%) were significantly different from each other and from E, T, and B. The EC50 values were converted to ED50 in nmols. Relative anesthetic potency, defined as the inverse value of ED50 of drug was 23:16:15:2.4:1 for B, E, T, L, and P, respectively. ED50 showed high correlation (R = 0.978) with partition coefficients of local anesthetics. This study implies that the partition coefficient is a predictor of intrathecal local anesthetic potency. We suggest that the mouse model is reliable for evaluation of intrathecal local anesthetic action.
Langerman
L
L
Department of Anesthesiology, New York University Medical Center, New York.
Bansinath
M
M
Grant
G J
GJ
D000775:Anesthesia, Spinal; D000779:Anesthetics, Local / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D012995:Solubility
D000779:Anesthetics, Local