Dermal effects and pharmacokinetic evaluation of the lidocaine/prilocaine cream in healthy Chinese volunteers

Abstract

Background: EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers.

Materials and methods: The Pharmacokinetics of the lidocaine/prilocaine test (T) or reference (R, EMLA) cream were evaluated in a fasting, single-dose, two-period crossover bioequivalent study conducted in 40 healthy Chinese volunteers. Meanwhile, the dermal effects including blanching, erythema, temperature sensation, edema, and skin rash were also evaluated during the study.

Results: After applied 15 g of the cream for 4 h to a 100 cm² area under plastic occlusive film on the skin of the thigh of healthy volunteers, the results of the pharmacokinetic study showed that the active components absorbed in skin from topical products was relatively low compared with most system absorption drugs. After the removal of the residual anesthetic cream, there was a vascular biphasic response with initial transient blanching which reaches a peak at 4.5 h and later more persisting period erythema. The change of temperature sensory sensitivity reached the peak value at 4.5-6 h.There was no statistically significant difference of the changes after application the lidocaine/prilocaine T or R cream in subjects. In general, the lidocaine/prilocaine T or R cream was well tolerated.

Conclusion: The method described a model for investigations of pharmacokinetics and pharmacodynamics of topical lidocaine/prilocaine cream. Except the plasma drug level indicator, these pharmacodynamics data should also be evaluated in the anesthetic transdermal pharmacokinetics study.

Clinical trial registration: CTR20211544; registered in http://www.chinadrugtrials.org.cn/ at September 2021.

Keywords: Dermal Effects; EMLA; Pharmacokinetic Evaluation.

Fig. 1

The mean plasma concentration-time curves of lidocaine

Fig. 2

The mean plasma concentration-time curves of prilocaine

Fig. 3

The cold and hot sensation change after application the lidocaine/prilocaine test or reference cream

Fig. 4

Spearman correlation test of the skin blanching reaction between the test or reference cream evaluated by colorimeter (x) and naked eyes (y)

Fig. 5

Spearman correlation test between the skin erythema reaction evaluated by colorimeter (x) and naked eyes (y)

Fig. 6

The skin blanching reaction values of lidocaine/prilocaine test or reference cream evaluated by colorimeter

Fig. 7

The skin erythema reaction values of lidocaine/prilocaine test or reference cream evaluated by colorimeter