Pharmacokinetic study of liposome-encapsulated and plain mepivacaine formulations injected intra-orally in volunteers.
OBJECTIVE
The pharmacokinetics of commercial and liposome-encapsulated mepivacaine (MVC) injected intra-orally in healthy volunteers was studied.


METHODS
In this double blind, randomized cross-over study, 15 volunteers received, at four different sessions, 1.8 ml of the following formulations: 2% MVC with 1 : 100 000 epinephrine (MVC(2%EPI) ), 3% MVC (MVC(3%) ), 2% and 3% liposome-encapsulated MVC (MVC(2%LUV) and MVC(3%LUV) ). Blood samples were collected pre dose (0 min) and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360 min after injections. Liquid chromatography-tandem mass spectrometry was used to quantify plasma MVC concentrations.


RESULTS
Pharmacokinetic analysis showed that the maximum plasma concentration (Cmax) and the areas under the curves (AUC(0-360) and AUC(0-∞)) after MVC(2%LUV) and MVC(2%EPI) injections were smaller (P < 0.05) than the equivalent figures for MVC(3%) and MVC(3%LUV). The time to maximum plasma concentration (Tmax) and the half-life of elimination (t½beta) obtained after the treatment with MVC(2%LUV), MVC(2%EPI), MVC(3%) and MVC(3%LUV) presented no statistically significant differences (P > 0.05). Cmax, AUC(0-360) and AUC(0-∞) after injection of the 2% formulations (MVC(2%LUV) and MVC(2%EPI) ) did not exhibit statistically significant differences (P > 0.05). The pharmacokinetics of MVC(2%LUV) were comparable to the pharmacokinetics of MVC(2%EPI).


CONCLUSIONS
The liposomal formulation of 2% MVC exhibits similar systemic absorption to the local anesthetic with vasoconstrictor.
São Francisco University, Bragança Paulista, Brazil. giovana.tofoli@saofrancisco.edu.br
Giovana Radomille
GR
Tofoli
Cíntia M S
CM
Cereda
Daniele Ribeiro
DR
Araújo
Michelle
M
Franz-Montan
Francisco Carlos
FC
Groppo
Daiane
D
Quaglio
Jose
J
Pedrazzoli Junior
Silvana Aparecida
SA
Calafatti
Fabio Alessandro Proença
FA
Barros
Eneida
E
de Paula
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004837:Epinephrine / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D007267:Injections; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008619:Mepivacaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D055815:Young Adult
D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D008081:Liposomes; D014662:Vasoconstrictor Agents; D008619:Mepivacaine; D004837:Epinephrine