Pharmacokinetics Of Lidocaine Research Articles

Lidocaine pharmacokinetics in postmenopausal women on hormone therapy

The study was designed to evaluate the effect of hormone therapy (HT) preparations containing 17beta-estradiol and micronized progesterone administered orally and transdermally on the pharmacokinetics of lidocaine, a probe drug that is metabolized by liver oxidative pathways involving cytochrome P-450 1A2 and 3A4 (CYP1A2 and CYP3A4). The study was carried out in 18 postmenopausal women divided into two groups administered HT for 6 months: group 1, 17beta-estradiol (orally) and micronized progesterone sublingually; and group 2, 17beta-estradiol (transdermally) and micronized progesterone sublingually. Pharmacokinetic study with intravenous lidocaine (1 mg/kg) and blood sampling during 360 minutes from injection was performed before the HT initiation and after 3 and 6 months of HT. Pharmacokinetic parameters of lidocaine demonstrated accelerated drug elimination in women on oral HT after 3 months. A significant reduction of area under the curve by 15.0% (P < 0.05), shortening of t(1/2) by 15.2% (P < 0.05), increase of lambda(z) by 10.0% (P < 0.05), and Cl/BW by 14.3% (P < 0.05) were observed. In contrast, transdermal administration of HT did not influence pharmacokinetic parameters of the drug. The effects of oral HT were not seen 6 months after the start of HT. HT can influence the pharmacokinetics of lidocaine, ie, its hepatic metabolism, through CYP3A4 and CYP1A2. The effect depends on the route of administration and therapy duration.

Effect of Fluvoxamine and Erythromycin on the Pharmacokinetics of Oral Lidocaine

Lidocaine is metabolized by cytochrome P450 3A4 (CYP3A4) and CYP1A2 enzymes, but inhibitors of CYP3A4 have had only a minor effect on its pharmacokinetics. We studied the effect of co-administration of fluvoxamine (CYP1A2 inhibitor) and erythromycin (CYP3A4 inhibitor) on the pharmacokinetics of lidocaine in a double-blind, randomized, three-way cross-over study. Eight healthy volunteers ingested daily either 100 mg fluvoxamine and placebo, 100 mg fluvoxamine and 1500 mg erythromycin, or their corresponding placebos (control) for five days. On day 6, 1 mg/kg lidocaine was administered orally. Plasma concentrations of lidocaine, monoethylglycinexylidide (MEGX) and 3-hydroxylidocaine (3-OH-lidocaine) were measured for 10 hr. During the fluvoxamine phase the area under the plasma concentration-time curve (AUC) and peak concentration (Cmax) of oral lidocaine were 305% (P<0.001) and 220% (P<0.05) of the control values. During the combination of fluvoxamine and erythromycin, lidocaine AUC was 360% (P<0.001) and Cmax 250% (P<0.05) of those during placebo. Fluvoxamine alone had no statistically significant effect on the half-life of lidocaine (t1/2), but during the combination phase t1/2 (3.8 hr) was significantly longer than during the placebo phase (2.4 hr; P<0.01). Fluvoxamine alone and in the combination with erythromycin decreased MEGX peak concentrations by approximately 50% (P<0.001) and 30% (P<0.01), respectively. We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces the presystemic metabolism of oral lidocaine and may increase the risk of lidocaine toxicity if lidocaine is ingested. The concomitant use of both fluvoxamine and a CYP3A4 inhibitor like erythromycin may further increase plasma lidocaine concentrations.

Influence of gastrointestinal tract disease on pharmacokinetics of lidocaine after intravenous infusion in anesthetized horses

Influence of gastrointestinal tract disease on pharmacokinetics of lidocaine after intravenous infusion in anesthetized horses

Influence of gastrointestinal tract disease on pharmacokinetics of lidocaine after intravenous infusion in anesthetized horses

To determine the disposition of lidocaine after IV infusion in anesthetized horses undergoing exploratory laparotomy because of gastrointestinal tract disease. 11 horses (mean +/- SD, 10.3 +/- 7.4 years; 526 +/- 40 kg). Lidocaine hydrochloride (loading infusion, 1.3 mg/kg during a 15-minute period [87.5 microg/kg/min]; maintenance infusion, 50 microg/kg/min for 60 to 90 minutes) was administered IV to dorsally recumbent anesthetized horses. Blood samples were collected before and at fixed time points during and after lidocaine infusion for analysis of serum drug concentrations by use of liquid chromatography-mass spectrometry. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. Selected cardiopulmonary variables, including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2, were recorded. Recovery quality was assessed and recorded. Serum lidocaine concentrations paralleled administration, increasing rapidly with the initiation of the loading infusion and decreasing rapidly following discontinuation of the maintenance infusion. Mean +/- SD volume of distribution at steady state, total body clearance, and terminal half-life were 0.70 +/- 0.39 L/kg, 25 +/- 3 mL/kg/min, and 65 +/- 33 minutes, respectively. Cardiopulmonary variables were within reference ranges for horses anesthetized with inhalation anesthetics. Mean HR ranged from 36 +/- 1 beats/min to 43 +/- 9 beats/min, and mean MAP ranged from 74 +/- 18 mm Hg to 89 +/- 10 mm Hg. Recovery quality ranged from poor to excellent. Availability of pharmacokinetic data for horses with gastrointestinal tract disease will facilitate appropriate clinical dosing of lidocaine.

Effects of intravenous administration of lidocaine on the thermal threshold in cats

To determine the effects of IV administration of lidocaine on thermal antinociception in conscious cats. 6 cats. 2 experiments were performed in each cat (interval of at least 2 months). In experiment 1, lidocaine pharmacokinetics were determined for each conscious cat following IV administration of a bolus of lidocaine (2 mg/kg). In experiment 2, data from experiment 1 were used to calculate appropriate doses of lidocaine that would achieve predetermined plasma lidocaine concentrations in the cats; lidocaine (or an equivalent volume of saline [0.9% NaCl] solution as the control treatment) was administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1, 2, 5, and 8 microg/mL. Skin temperature and thermal threshold were determined at the start of the experiment (baseline) and at each concentration. Samples of venous blood were obtained at each target concentration for plasma lidocaine concentration determination. In experiment 2, actual plasma lidocaine concentrations were 0.00 +/- 0.00 microg/mL, 0.25 +/- 0.18 microg/mL, 0.57 +/- 0.20 microg/mL, 1.39 +/- 0.13 microg/mL, 2.33 +/- 0.45 microg/mL, and 4.32 +/- 0.66 microg/mL for target plasma concentrations of 0, 0.5, 1, 2, 5, and 8 microg/mL, respectively. Compared with baseline values, no significant change in skin temperature or thermal threshold was detected at any lidocaine plasma concentration (or saline solution equivalent). Skin temperature or thermal threshold values did not differ between lidocaine or control treatments. Results indicated that these moderate plasma concentrations of lidocaine did not affect thermal antinociception in cats.

Effect of ciprofloxacin on the pharmacokinetics of intravenous lidocaine

Recent studies have suggested that cytochrome P-450 isoenzyme 1A2 has an important role in lidocaine biotransformation. We have studied the effect of a cytochrome P-450 1A2 inhibitor, ciprofloxacin, on the pharmacokinetics of lidocaine. In a randomized, double-blinded, cross-over study, nine healthy volunteers ingested for 2.5 days 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 1.5 mg kg[-1] lidocaine intravenously over 60 min. Plasma concentrations of lidocaine, 3-hydroxylidocaine and monoethylglycinexylidide were determined for 11 h after the start of the lidocaine infusion. Ciprofloxacin increased the mean peak concentration and area under plasma concentration-time curve of lidocaine by 12% (range [-6] to+46%; P<0.05) and 26% (8--59%; P 0.01), respectively. The mean plasma clearance of lidocaine was decreased by ciprofloxacin by 22% (7--38%; P<0.01). Ciprofloxacin decreased the area under the plasma concentration-time curve of monoethylglycinexylidide by 21% (P<0.01) and that of 3-hydroxylidocaine by 14% (P< 0.01). The plasma decay of intravenously administered lidocaine is modestly delayed by concomitantly administered ciprofloxacin. Ciprofloxacin may increase the systemic toxicity of lidocaine.

Pharmacokinetics of lidocaine and its active metabolite, monoethylglycinexylidide, after intravenous administration of lidocaine to awake and isoflurane-anesthetized cats

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. 8 healthy adult cats. 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. 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. 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.

The Effect of Erythromycin and Fluvoxamine on the Pharmacokinetics of Intravenous Lidocaine

Inhibitors of CYP3A4 (cytochrome P450 3A4) have a minor effect on lidocaine pharmacokinetics. We studied the effect of coadministration of the antidepressant fluvoxamine (CYP1A2 inhibitor) and antimicrobial drug erythromycin (CYP3A4 inhibitor) on lidocaine pharmacokinetics in a double-blind, randomized, three-way crossover study. Nine volunteers ingested daily 100 mg fluvoxamine and placebo, 100 mg fluvoxamine and 1500 mg erythromycin, or their corresponding placebos for 5 days. On day 6, 1.5 mg/kg lidocaine was administered IV over 60 min. Concentrations of lidocaine and its major metabolite monoethylglycinexylidide were measured for 10 h. Fluvoxamine alone decreased the clearance of lidocaine by 41% (P < 0.001) and prolonged its elimination half-life from 2.6 to 3.5 h (P < 0.01). During the combination of fluvoxamine and erythromycin, lidocaine clearance was 53% smaller than during placebo (P < 0.001) and 21% smaller than during fluvoxamine alone (P < 0.05). During the combination phase the half-life of lidocaine (4.3 h) was longer than during the placebo (2.6 h; P < 0.001) or fluvoxamine (3.5 h; P < 0.01). We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces elimination of lidocaine and may increase the risk of lidocaine toxicity. Concomitant use of both fluvoxamine and a CYP3A4 inhibitor such as erythromycin can further increase plasma lidocaine concentrations by decreasing its clearance.

Pharmacokinetics of lidocaine and tetracaine following a single application of the LT peel (lidocaine 7% and tetracaine 7% cream)

Pharmacokinetics of lidocaine and tetracaine following a single application of the LT peel (lidocaine 7% and tetracaine 7% cream)

Pharmacokinetics of combined intraperitoneal and incisional lidocaine in the dog following ovariohysterectomy

Topical application of local anesthetics provides safe analgesia following abdominal surgery in people. Conservative doses have been utilized to avoid toxicity. Toxic effects are proportional to amount of drug administered and the plasma concentration of the drug, allowing predictions of safety following pharmacokinetic studies. The maximum plasma level, the pharmacokinetics and the safety of lidocaine hydrochloride when administered by the combined intraperitoneal (8 mg/kg i.p. with epinephrine 1:400 000) and incisional (2 mg/kg with epinephrine 1:200 000) routes were studied in six mixed breed dogs following ovariohysterectomy. Rapid uptake of lidocaine produced a peak concentration of 1.45 +/- 0.36 microg/mL (mean +/- SD, range 0.80-1.86 microg/mL) by 0.37 +/- 0.26 h (range 0.11-0.81) after administration. The absorption half-life was 0.13 +/- 0.1 h. Plasma concentrations decreased rapidly and the elimination half-life was 1.17 +/- 0.11 h. No signs of toxicity were observed in these dogs in the 18 h following drug administration. The dose studied generated levels of lidocaine well below toxic.

Cytochrome P450 1A2 is a major determinant of lidocaine metabolism in vivo: effects of liver function

This study was designed (1) to evaluate the effect of a cytochrome P450 (CYP) 1A2 inhibitor, fluvoxamine, on the pharmacokinetics of intravenous lidocaine and its 2 pharmacologically active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), to confirm recent in vitro results indicating that CYP1A2 is the main isoform responsible for lidocaine biotransformation and (2) to assess whether liver function has any influence on the fluvoxamine-lidocaine interaction. The study was carried out in 10 healthy volunteers and 20 patients with cirrhosis, 10 with mild (Child grade A) and 10 with severe (Child grade C) liver dysfunction, according to a randomized, double-blind, 2-phase, crossover design. In one phase all participants received placebo for 6 days; in the other phase they received 50 mg fluvoxamine for 2 days and 100 mg fluvoxamine for the next 4 days. On day 6, a 1-mg/kg lidocaine dose was administered intravenously 2 hours after the last dose of fluvoxamine or placebo. Plasma concentrations of lidocaine, MEGX, GX, and fluvoxamine were measured up to 12 hours after lidocaine injection. The effects of fluvoxamine coadministration were dependent on liver function. Lidocaine clearance was decreased on average by 60% (from 12.1 mL/min.kg to 4.85 mL/min.kg, P <.001) in healthy subjects and by 44% (from 9.83 mL/min.kg to 5.06 mL/min.kg, P <.001) in patients with mild liver dysfunction, with proportional increases in terminal half-lives, whereas virtually no effect was produced in patients with severe liver dysfunction (4.21 mL/min.kg versus 3.65 mL/min.kg, P >.05). Analogous effects were observed on MEGX and GX formation kinetics, which were drastically impaired in healthy subjects and patients with mild liver cirrhosis but virtually unaffected in patients with severe cirrhosis. CYP1A2 is the enzyme principally responsible for the metabolic disposition of lidocaine in subjects with normal liver function. The extent of fluvoxamine-lidocaine interaction decreases as liver function worsens, most likely because of the concomitant decrease in the hepatic level of CYP1A2. These observations indicate that results obtained in healthy subjects cannot be extended a priori to patients with liver dysfunction, but the clinical consequences of inhibition of drug metabolism must also be assessed in such patients.

Free lidocaine concentrations during continuous epidural anesthesia in geriatric patients

Background and Objectives: To evaluate the effects of aging on lidocaine pharmacokinetics, the plasma concentrations of total and free lidocaine and its metabolites were measured during continuous thoracic epidural anesthesia in middle-aged (age 41 ± 9 years, n = 7) and elderly (age 72 ± 2 years, n = 7) male patients. Methods: After establishment of general anesthesia, 7 mL 1.5% lidocaine with epinephrine 1:200,000 was injected into the epidural space and subsequently infused at a rate of 5 mL/h for 5 hours. Plasma concentrations of total and free lidocaine, monoethylglycinexylidide (MEGX), and glycinexylidide (GX) were measured at 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, and 300 minutes after initial lidocaine injection using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results: The elderly group showed a stronger upward trend in the corrected free lidocaine concentrations and lower corrected total MEGX concentrations than the middle-aged group. Conclusions: Lidocaine metabolite activity in the elderly male patients was lower than that in the middle-aged male patients. Free lidocaine concentration is prone to increase in elderly patients. Caution must be exercised during continuous thoracic epidural anesthesia combined with general anesthesia in geriatric patients. Reg Anesth Pain Med 2003;28:215-220.

Effect of glycerol-induced acute renal failure on the pharmacokinetics of lidocaine after transdermal application in rats.

In this study, the effect of glycerol-induced acute renal failure (ARF) on the pharmacokinetics of lidocaine after transdermal application was investigated in rats. Microdialysis method was applied in vitro and in vivo to the abdominal skin of rats. After topical application of 1% lidocaine, the cumulative amount of lidocaine permeated through the excised rat abdominal skin showed parallel effect between normal and ARF rats with no significant difference in the in vitro permeability coefficient of lidocaine between them, while area under the plasma concentration versus time curve of lidocaine in ARF rats increased significantly. The protein binding rate of lidocaine in ARF plasma and the blood vessel permeability to muscle tissues, assessed by beta-D-glucopyranosyl fluorescein isothiocyanate-labeled (FITC) albumin, increased significantly. After intravenous infusion of 5 mg/h/kg lidocaine, both of the total body clearance and the volume of distribution of lidocaine in the ARF rats decreased significantly. These results suggested that renal dysfunction did not have any effect on the skin permeability of lidocaine, but might change the plasma protein binding of drug and blood vessel permeability which led to high plasma concentration of lidocaine.

Modeling population pharmacokinetics of lidocaine: should cardiac output be included as a patient factor?

Inclusion of cardiac output and other physiologic parameters, in addition to or instead of, demographic variables might improve the population pharmacokinetic modeling of lidocaine. Thirty-one patients were included in a population pharmacokinetic study of lidocaine. After bolus injection of lidocaine (1 mg/kg), 22 or 10 blood samples per patient were taken from a radial artery. During the experiment, cardiac output was measured using a thoracic electrical bioimpedance method. The following four population pharmacokinetic models were constructed and their performances investigated: a model with no covariates, a model with cardiac output as covariate, a model with demographic covariates, and a model with both cardiac output and demographic characteristics as covariates. Model discrimination was performed with the likelihood ratio test. Inclusion of cardiac output resulted in a significant improvement of the pharmacokinetic model, but inclusion of demographic covariates was even better. However, the best model was obtained by inclusion of both demographic covariates and cardiac output in the pharmacokinetic model. When population pharmacokinetic models are used for individualization of dosing schedules, physiologic covariates, e.g., cardiac output, can improve their ability to predict the individual kinetics.

Perioperative management of cosmetic liposuction.

Recent qualms about the safety of aesthetic lipoplasty may be attributable more to support system flaws than to technical process deficiencies. The authors here focus on perfunctory patient monitoring when sedative or analgesic drugs are given, cavalier infiltration of mega-dose lidocaine, cursory intraoperative patient observation by team members with conflicting responsibilities, anesthesia providers unfamiliar with the unique surgical physiology of liposuction, hurried-discharge policies that virtually ignore the residual depressant effects of sedatives and analgesics, and compressive dressings that impair postoperative chest-wall expansion and venous return. Whereas pulmonary embolism remains the leading process cause of morbidity from liposuction, complications from austere resource allocation to dedicated patient monitoring should be largely preventable. Not all lipoplasties require an anesthesia provider but-when heavy sedation, mega-dose lidocaine, or both, are projected-a trained team member dedicated exclusively to patient safety and comfort should be a minimum patient care standard. The potential role of lidocaine cardiotoxicity in tumescent anesthesia is widely underappreciated and that of hypothermia goes mostly unrecognized. These, plus largely preventable or potentially correctable perioperative events such as pulmonary edema, fluid imbalance, or improperly administered sedative and analgesic drugs, demand upgrading and expansion of monitoring, resuscitative, and recuperative facilities in physician offices. In fact, ASPS guidelines urge that anesthesia services be engaged for dedicated patient care whenever "major" liposuction or conscious sedation is projected, because liposuction is neither as benign nor as simple a procedure as heretofore reputed. To assess objectively the operative and anesthetic risk of obesity, document body mass index for the preoperative record; morbid obesity (body mass index >/= 35.0), for instance, is a known risk multiplier for sedatives and analgesics. Other system issues such as the dynamic profile of high-dose lidocaine pharmacokinetics, the deportation of fat globules in the bloodstream, and the incidence of intraoperative hypothermia remain as unresolved topics for interdisciplinary, multi-institutional clinical research.

The effects of norepinephrine and prostaglandin E 1 on pharmacokinetics of lidocaine in isolated perfused rat liver

We hypothesized that depression of liver function by norepinephrine can be improved by prostaglandin E 1. Isolated perfused rat liver was selected as an experimental model, since the flow rate can be regulated in it. Twenty-one rats were randomly allocated to three groups: control, norepinephrine, and norepinephrine and prostaglandin E 1 groups. The liver was perfused in a recirculating system at a constant flow rate of 20 ml/min. After administration of two milligrams of lidocaine in each group, lidocaine and monoethylglycinexylidide concentrations in the recirculating system were measured. Lidocaine pharmacokinetics were analyzed using the SAAM II ® program, including metabolic rate from lidocaine to monoethylglycinexylidide using time-concentration curves. Norepinephrine significantly increased perfusion pressure and the area under the time-concentration curve for lidocaine. Norepinephrine decreased the clearance and the elimination rate constant of lidocaine compared with those in the control group. Although administration of prostaglandin E 1 after infusion of norepinephrine did not significantly change perfusion pressure, it significantly (p < 0.05) improved metabolic rate, clearance and the elimination rate constant of lidocaine in the isolated rat liver model.

Spinal biopharmaceutics of bupivacaine and lidocaine by microdialysis after their simultaneous administration in rabbits

The aim of the present study was to determine the intrathecal bioavailability of a mixture of lidocaine and bupivacaine in a rabbit model of spinal anesthesia by using the microdialysis technique. Catheter and microdialysis probe were inserted under control of the view either in the epidural or in the intrathecal space. First, the epidural disposition of the mixture of bupivacaine and lidocaine was studied after epidural administration. Then, the intrathecal and plasma dispositions of bupivacaine and lidocaine were investigated following intrathecal or epidural administration. The epidural clearance of bupivacaine was higher than that of lidocaine, suggesting a more significant uptake of bupivacaine into the systemic circulation and/or into the CSF. The intrathecal bioavailability of bupivacaine and lidocaine was 12.3 and 17.9%, respectively, while it was 5.5 and 17.7% following the separate administration of each agent [Clément, R., Malinovsky, J.M., Le Corre, P., Dollo, G., Chevanne, F., Le Verge, R., 1999. Cerebrospinal fluid bioavailability and pharmacokinetics of bupivacaine and lidocaine following intrathecal and epidural administrations in rabbits using microdialysis. J. Pharmacol. Exp. Ther. 289, 1015–21]. After intrathecal administration, a decrease in C max and AUC values was observed for bupivacaine in comparison with the separate administration. Moreover, after epidural administration, the systemic resorption was slower and lower, especially for bupivacaine. Such a reduction in the systemic absorption of bupivacaine might increase its intrathecal bioavailability, resulting from a vasoconstrictor effect of lidocaine reducing the systemic absorption of bupivacaine from the epidural space leading to an increase of its extent of absorption through meninges into CSF although its absorption rate was not modified.

Plasma lidocaine, monoethylglycinexylidide, and glycinexylidide concentrations after epidural administration in geriatric patients

Background and Objectives: The purpose of this study was to evaluate the effect of age on the pharmacokinetics of lidocaine after epidural administration. Methods: Two percent lidocaine with epinephrine (5 μg/mL) was administered in two different age groups: an adult group (age 42 ± 6 years, n = 10) and an elderly group (age 77 ± 4 years, n = 10). Concentrations of lidocaine and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in plasma samples obtained after 15, 30, 45, 60, 90, 120, 150, and 180 minutes of administration using high-performance liquid chromatography with ultraviolet detection. Results: No significant differences in plasma concentrations of lidocaine and its metabolites were observed between the two groups during the 3 hours of study. However, the elderly group showed significantly longer mean residence times (MRTs) and lower plasma clearance of lidocaine during the period compared with the adult group ( P < .05). Plasma concentration ratios of MEGX/lidocaine were significantly lower in the elderly group after 2 hours of lidocaine administration ( P < .05). Conclusions: The increase in plasma lidocaine concentration after epidural anesthesia in elderly patients was not as high as anticipated. However, the elderly patients showed longer MRTs, lower clearance, and lower ratios of MEGX/lidocaine than did the adult (middle-age) patients. Reg Anesth Pain Med 2000;25:268–273.

The pharmacokinetics of morphine and lidocaine in nine severe trauma patients

Study Objective: To study the pharmacokinetic parameters of morphine and lidocaine after a single intravenous (IV) bolus in severe trauma patients. Design: Clinical case study. Setting: Department of Anesthesiology and Intensive Care of a university hospital. Patients: Nine patients, ages 24 to 91 years (mean 54.4 yrs), admitted to the hospital with severe trauma (Injury Severity Score >20) were included in the study. Interventions: After initial evaluation and stabilization, a single IV dose of morphine 0.025 mg/kg and lidocaine 1.5 mg/kg was given separately, and blood samples were drawn for each drug serum concentration. Measurements and Main Results: Morphine pharmacokinetics was studied in eight patients, lidocaine pharmacokinetics in seven patients, and both drugs were studied in six patients. Morphine clearance 2.5 to 10 ml/kg/min (6 ± 2.6, mean ± SD) and volume of distribution 0.28 to 3.30 L/kg (1.4 ± 1.0) were found to be lower than values described previously for healthy volunteers (33.5 ± 9 ml/kg/min and 5.16 ± 1.40 L/kg, respectively), and are similar to those described in trauma patients (5 ± 2.9 ml/kg/min and 0.9 ± 0.2 L/kg, respectively). In contrast, lidocaine clearance 4.5 to 9.4 ml/kg/min (6.7 ± 1.7) and volume of distribution 0.39 to 1.20 L/kg (0.72 ± 0.28) were similar to the value described in healthy volunteers (10 ml/kg/min and 1.32 L/kg, respectively). Conclusion: Changes in pharmacokinetics of drugs eliminated by the liver may occur in patients with severe trauma. The preserved lidocaine clearance indicates an almost normal hepatic blood flow and suggests that other mechanisms may be involved in the lower morphine clearance. The findings may have applications for the treatment of severe trauma patients and suggest that drug monitoring might be needed in some instances so as to avoid toxicity.

Population pharmacokinetics of lidocaine in Korean adults during general anesthesia1

Population pharmacokinetics of lidocaine in Korean adults during general anesthesia1