Pharmacokinetics of lidocaine and its metabolite in peridural anesthesia administered to pregnant women with gestational diabetes mellitus.
BACKGROUND
Peridural blockade with lidocaine, bupivacaine, and fentanyl is an anesthetic procedure extensively used in obstetrics, justifying the pharmacokinetic study of these drugs during labor.


OBJECTIVE
To investigate the influence of the physiopathological changes of gestational diabetes mellitus (GDM) on the pharmacokinetics of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in pregnant women subjected to peridural anesthesia.


METHODS
Ten normal pregnant women (group 1) and six pregnant women with GDM (group 2) were studied, all of them at term. The patients received 200 mg 2% lidocaine hydrochloride without a vasoconstrictor by the peridural locoregional route. Maternal blood samples were collected at predetermined times for the analysis of lidocaine and MEGX by chromatography and pharmacokinetic analysis.


RESULTS
The median pharmacokinetic parameters of lidocaine for groups 1 and 2 (P </= 0.05), respectively, were as follows: for Cmax 879.11 and 1,145.58 ng/ml, AUC(0-infinity) 256.01 and 455.95 mug min(-1) ml(-1), Cl/f/kg 10.61 and 5.64 ml min(-1) kg(-1), and Vd/f/kg 3.26 and 2.19 L/kg. The median pharmacokinetic parameters of MEGX for groups 1 and 2 (P </= 0.05), respectively, were as follows: for Cmax 82.71 and 141.38 ng/ml, Tmax 44.71 and 193.14 min, t(1/2)alpha 7.64 and 59.77 min, alpha 0.097 and 0.012/min, and AUC(0-infinity) 29.91 and 108.23 mug min(-1) ml(-1).


CONCLUSIONS
The present data permit us to conclude that the apparent clearance of lidocaine and MEGX was reduced in diabetic patients compared to normal women, suggesting that GDM inhibits the CYP1A2/CYP3A4 isoforms responsible for the metabolism of this drug and its metabolite.
Moisés
Elaine Christine Dantas
EC
University Hospital, Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. elainemoises@hcrp.fmrp.usp.br
Duarte
Luciana de Barros
Lde B
Cavalli
Ricardo de Carvalho
Rde C
Marques
Maria Paula
MP
Lanchote
Vera Lúcia
VL
Duarte
Geraldo
G
da Cunha
Sérgio Pereira
SP
D000328:Adult; D000767:Anesthesia, Epidural; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D016640:Diabetes, Gestational / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D011247:Pregnancy; D013997:Time Factors; D055815:Young Adult
D000779:Anesthetics, Local; D008012:Lidocaine; C001173:monoethylglycinexylidide; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human