Pharmacokinetics of lidocaine and its metabolite in peridural anesthesia administered to pregnant women with gestational diabetes mellitus
2008
Moisés, Elaine Christine Dantas | Duarte, Luciana de Barros | Cavalli, Ricardo de Carvalho | Marques, Maria Paula | Lanchote, Vera Lúcia | Duarte, Geraldo | da Cunha, Sérgio Pereira
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. Patients and 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, AUC₀₋[infinity] 256.01 and 455.95 μg 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, t₁/₂α 7.64 and 59.77 min, α 0.097 and 0.012/min, and AUC₀₋[infinity] 29.91 and 108.23 μg min⁻¹ ml⁻¹. Conclusion 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.
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