Mepivacaine Hydrochloride

Mepivacaine is an intermediate-acting amide local anesthetic widely used in dentistry since the 1960s. It is structurally a pipecholyl xylidine, similar to bupivacaine. Compared to lidocaine, mepivacaine has lower lipid solubility and hydrophobicity, yet similar clinical efficacy. Its pKa of 7.6 is slightly lower than lidocaine, theoretically offering better performance in infected tissues. Mepivacaine is available with or without the vasoconstrictor levonordefrin.
Unlike lidocaine, mepivacaine with levonordefrin does not significantly reduce systemic absorption; serum levels remain similar to plain formulations. Mepivacaine is metabolized primarily by CYP1A2 via hydroxylation to inactive metabolites. It has slower total body clearance (0.45 L/min) compared to lidocaine (0.95-1.1 L/min), making it more susceptible to accumulation with repeat dosing, particularly in young children (under 5 years) where CYP1A2 activity is immature.

Fig. 1 Mepivacaine metabolism. (Brockmann W G. 2014)

Mepivacaine, a local anesthetic with intrinsic vasoconstrictor activity, was formulated into clear, non-greasy topical microemulsion-based gels. Microemulsions were developed using oleic acid as the oil phase, Labrasol and Transcutol P (1:1) as surfactant/cosurfactant, and water. Carbopol 980 was added as a gelling matrix to improve viscosity. Formulations were characterized for globule size, polydispersity index, zeta potential, stability, and viscosity. Microstructure was analyzed by NMR, small-angle neutron scattering, conductivity, and DSC. In vitro diffusion across porcine skin using Franz cells showed that microemulsion-based hydrogels increased mepivacaine flux several-fold compared to conventional gels. Oleic acid provided both excellent drug solubility and skin permeation enhancement.