OBJECTIVE: To describe the pharmacokinetics of lidocaine and its active metabolite, monoethylglycinexylidide (MEGX), after i.v. administration of a single bolus of lidocaine in cats that were awake in phase 1 and anesthetized with isoflurane in phase 2 of the study. ANIMALS: 8 healthy adult cats. PROCEDURE: During phase 1, cats were administered lidocaine (2 mg/kg, i.v.) as a bolus injection (time 0). During phase 2, cats were anesthetized with isoflurane and maintained at 0.75 times the minimum alveolar concentration of isoflurane for each specific cat. After a 15-minute equilibration period, lidocaine (2 mg/kg, i.v.) was administered as a bolus injection to each cat (time 0). In both phases, plasma concentrations of lidocaine and MEGX were measured at various time points by use of liquid chromatography-mass spectrometry. RESULTS: Anesthesia with isoflurane significantly decreased the volume of the central compartment, clearance, and elimination half-life of lidocaine and significantly increased the extrapolated plasma drug concentration at time 0, compared with values for awake cats. Pharmacokinetics of MEGX were also changed by isoflurane-induced anesthesia because the maximum observed plasma concentration (C(max)), area under the concentration-time curve extrapolated to infinity, and time to C(max) were significantly higher in anesthetized cats, compared with values for awake cats. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetics of lidocaine and MEGX were substantially altered in cats anesthetized by use of isoflurane. When pharmacokinetic variables are used to determine loading and infusion doses in awake or anesthetized cats, they should be measured in cats that are awake or anesthetized, respectively.
OBJECTIVE: To describe the pharmacokinetics of lidocaine and its active metabolite, monoethylglycinexylidide (MEGX), after i.v. administration of a single bolus of lidocaine in cats that were awake in phase 1 and anesthetized with isoflurane in phase 2 of the study. ANIMALS: 8 healthy adult cats. PROCEDURE: During phase 1, cats were administered lidocaine (2 mg/kg, i.v.) as a bolus injection (time 0). During phase 2, cats were anesthetized with isoflurane and maintained at 0.75 times the minimum alveolar concentration of isoflurane for each specific cat. After a 15-minute equilibration period, lidocaine (2 mg/kg, i.v.) was administered as a bolus injection to each cat (time 0). In both phases, plasma concentrations of lidocaine and MEGX were measured at various time points by use of liquid chromatography-mass spectrometry. RESULTS: Anesthesia with isoflurane significantly decreased the volume of the central compartment, clearance, and elimination half-life of lidocaine and significantly increased the extrapolated plasma drug concentration at time 0, compared with values for awake cats. Pharmacokinetics of MEGX were also changed by isoflurane-induced anesthesia because the maximum observed plasma concentration (C(max)), area under the concentration-time curve extrapolated to infinity, and time to C(max) were significantly higher in anesthetized cats, compared with values for awake cats. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetics of lidocaine and MEGX were substantially altered in cats anesthetized by use of isoflurane. When pharmacokinetic variables are used to determine loading and infusion doses in awake or anesthetized cats, they should be measured in cats that are awake or anesthetized, respectively.
Authors: Djo Hasan; Atsuko Shono; Coenraad K van Kalken; Peter J van der Spek; Eric P Krenning; Toru Kotani Journal: Purinergic Signal Date: 2021-11-10 Impact factor: 3.765