PMID- 33540917
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210316
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 13
IP  - 2
DP  - 2021 Feb 2
TI  - Evaluation of Lidocaine and Metabolite Pharmacokinetics in Hyaluronic Acid 
      Injection.
LID - 10.3390/pharmaceutics13020203 [doi]
LID - 203
AB  - Lidocaine-incorporated hyaluronic acid injection (LHA) is considered a promising 
      way to increase patient compliance. Various reviews and analyses have been 
      conducted to verify that the addition of lidocaine had no effect on the product 
      quality of hyaluronic acid injections. However, possible pharmacokinetic (PK) 
      alterations of lidocaine and its active metabolites, monoethylglycylxylidide 
      (MEGX) and glycylxylidide (GX), in hyaluronic acid injection have not been 
      studied so far. Thus, the objective of this study was to evaluate lidocaine and 
      its metabolite PK after 0.3% lidocaine solution or LHA injection and to 
      investigate any changes in PK profiles of lidocaine and its active metabolites. 
      To do this, a novel bio-analytical method for simultaneous determination of 
      lidocaine, MEGX, and GX in rat plasma was developed and validated. Then, plasma 
      concentrations of lidocaine and its active metabolites MEGX and GX following 
      subcutaneous (SC) injection of 0.3% lidocaine solution or LHA with 0.3-1% 
      lidocaine in male Sprague-Dawley rats were successfully determined. The obtained 
      data were used to develop a parent-metabolite pharmacokinetic (PK) model for LHA 
      injection. The half-life, dose-normalized C(max), and AUC(inf) of lidocaine after 
      SC injection of lidocaine solution and LHA did not show statistically significant 
      difference. The PK characteristics of lidocaine after LHA administration were 
      best captured using a two-compartment model with combined first-order and transit 
      absorption and its clearance described with Michaelis-Menten and first-order 
      elimination kinetics. Two one-compartment models were consecutively added to the 
      parent model for the metabolites. In conclusion, the incorporation of lidocaine 
      in hyaluronic acid filler injection did not alter the chemical's pharmacokinetic 
      characteristics.
FAU - Kim, Ju Hee
AU  - Kim JH
AD  - College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 
      Gyeonggi-do 13488, Korea.
FAU - Kang, Dong Wook
AU  - Kang DW
AD  - College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 
      Gyeonggi-do 13488, Korea.
FAU - Choi, Go-Wun
AU  - Choi GW
AD  - College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 
      Gyeonggi-do 13488, Korea.
FAU - Lee, Sang Bok
AU  - Lee SB
AD  - CHA Meditech Co., Ltd., Daejeon-si 1646, Korea.
FAU - Lee, Seongjin
AU  - Lee S
AD  - CHA Meditech Co., Ltd., Daejeon-si 1646, Korea.
FAU - Cho, Hea-Young
AU  - Cho HY
AUID- ORCID: 0000-0002-5995-6547
AD  - College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 
      Gyeonggi-do 13488, Korea.
LA  - eng
PT  - Journal Article
DEP - 20210202
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC7913210
OTO - NOTNLM
OT  - glycylxylidide
OT  - hyaluronic acid injection
OT  - lidocaine
OT  - modeling
OT  - monoethylglycylxylidide
OT  - parent-metabolite pharmacokinetic model
OT  - pharmacokinetics
COIS- The authors declare no conflict of interest. The company had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2021/02/06 06:00
MHDA- 2021/02/06 06:01
PMCR- 2021/02/02
CRDT- 2021/02/05 01:01
PHST- 2020/12/23 00:00 [received]
PHST- 2021/01/24 00:00 [revised]
PHST- 2021/01/28 00:00 [accepted]
PHST- 2021/02/05 01:01 [entrez]
PHST- 2021/02/06 06:00 [pubmed]
PHST- 2021/02/06 06:01 [medline]
PHST- 2021/02/02 00:00 [pmc-release]
AID - pharmaceutics13020203 [pii]
AID - pharmaceutics-13-00203 [pii]
AID - 10.3390/pharmaceutics13020203 [doi]
PST - epublish
SO  - Pharmaceutics. 2021 Feb 2;13(2):203. doi: 10.3390/pharmaceutics13020203.