Biomedical subjects

F Varin

Publications and source records attributed to F Varin.

At least 37 records · Page 2Linked to original sources

PubMed1998

Determination of ubiquinone-9 and 10 levels in rat tissues and blood by high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic (HPLC) method is presented for the simultaneous detection of ubiquinone-9 and 10 in rat tissues such as blood, myocardium, and muscle. After liquid-liquid extraction, the ubiquinones are subsequently analyzed by HPLC with ultraviolet (UV) detection at their maximum absorbance (275 nm). Reference calibration curves in ethanol are used to determine tissular levels of ubiquinones. Because a treatment with HMG-CoA reductase inhibitors is expected to decrease the ubiquinone levels, reference calibration curves are performed to ensure that the ratios (ubiquinone/internal standard) observed in such an experiment could be evaluated directly on a calibration curve. The assay is sensitive (0.0625 microgram/mL), reproducible (4% coefficient of variation for ubiquinone-9 and 6% for ubiquinone-10), and linear up to 20 micrograms/mL (or 100 mg of tissue) for ubiquinone-9 and up to 10 micrograms/mL (or 100 mg of tissue) for ubiquinone-10. The ubiquinone levels in control tissues or blood are within the ranges of those previously reported.

Animals↗

PubMed1998

Pharmacokinetics and pharmacodynamics of cisatracurium after a short infusion in patients under propofol anesthesia.

UNLABELLED: Fourteen patients, ASA physical status I or II, were recruited to assess the pharmacokinetic-pharmacodynamic relationship of cisatracurium under nitrous oxide/sufentanil/propofol anesthesia. The electromyographic response of the abductor digiti minimi muscle was recorded on train-of-four stimulation of the ulnar nerve. A 0.1-mg/kg dose of cisatracurium was given as an infusion over 5 min. Arterial plasma concentrations of cisatracurium and its major metabolites were measured by using high-performance liquid chromatography. A nontraditional two-compartment pharmacokinetic model with elimination from central and peripheral compartments was used. The elimination rate constant from the peripheral compartment was fixed to the in vitro rate of degradation of cisatracurium in human plasma (0.0237 min(-1)). The mean terminal half-life of cisatracurium was 23.9+/-3.3 min, and its total clearance averaged 3.7+/-0.8 mL x min(-1) x kg(-1). Using this model, the volume of distribution at steady state was significantly increased compared with that obtained when central elimination only was assumed (0.118+/-0.027 vs 0.089+/-0.017 L/kg). The effect-plasma equilibration rate constant was 0.054+/-0.013 min(-1). The 50% effective concentration (153+/-33 ng/mL) was 56% higher than that reported in patients anesthetized with volatile anesthetics, which suggests that, compared with inhaled anesthetics, a cisatracurium neuromuscular block is less enhanced by propofol. IMPLICATIONS: The drug concentration-effect relationship of the muscle relaxant cisatracurium has been characterized under balanced and isoflurane anesthesia. Because propofol is now widely used as an IV anesthetic, it is important to characterize the biological fate and the concentration-effect relationship of cisatracurium under propofol anesthesia as well.

Adolescent↗

PubMed1998

Clinical pharmacokinetics of neuromuscular relaxants in pregnancy.

Despite an increased in bodyweight, plasma volume by 45% and blood volume by 35% that might influence the volume of distribution of polar drugs, the apparent volume of distribution at steady state (Vss), volume of distribution (Vd) and the apparent volume of the central compartment (Vc) of atracurium, vecuronium and pancuronium are unchanged during pregnancy. With an elimination that is independent of renal, hepatic and enzymatic functions, the clearance of atracurium is also unchanged. This is corroborated by an unchanged clinical duration of atracurium during pregnancy. The clearance of pancuronium is increased by 27% during caesarean section. This may be explained by the increased glomerular filtration rate reported in pregnant women. The clinical duration of vecuronium in term and postpartum women is twice that reported in nonpregnant women. On the other hand, an increase in the clearance clearance of vecuronium during cesarean sections has been reported. The umbilical/maternal vein concentration ratio (UV/MV) of nondepolarising neuromuscular relaxants varies from 7 to 26% and clinical doses of these drugs may induce partial residual curarisation in neonates. Fetal concentrations of non-depolarising neuromuscular relaxants are proportional to the maternal dose injected as demonstrated for pancuronium and vecuronium. Increasing UV/MV with longer drug injection to delivery intervals have been demonstrated for drugs with a high molecular weight, such as atracurium, but not for those with a low molecular weight, such as vecuronium, while conflicting results have been reported for pancuronium. Despite decreased plasma pseudocholinesterases, the clinical duration of succinylcholine 1 mg/kg is unchanged in pregnant women, and only is slightly increased in postpartum women. On the other hand, larger doses of succinylcholine have induced prolonged apnoea and phase II block. The use of a pretreatment dose of a nondepolarising neuromuscular relaxant to decrease fasciculations and subsequent postoperative muscle pain is not only unnecessary in pregnant women but may be hazardous, since it may produce unexpected significant curarisation with respiratory distress. At clinical doses, transplacental passage of succinylcholine is insufficient to produce curarisation of neonates except in those born to mothers with abnormal plasma pseudocholinesterases. Magnesium sulfate, used in the treatment of pre-eclampsia, will enhance the blocking effects of nondepolarising neuromuscular relaxants but will have no effects on the characteristics of paralysis of succinylcholine. Histamine type 2 antagonists used to decrease the risk of aspiration during induction of anaesthesia do not influence the blocking properties of neuromuscular relaxants, while metoclopramide prolongs the block of succinylcholine.

Absorption↗

PubMed1997

Pharmacokinetic-pharmacodynamic modeling of doxacurium: effect of input rate.

One of the basic assumptions in pharmacokinetic-pharmacodynamic modeling (PK-PD) is that drug equilibration rate constant between plasma concentration and effect (Ke0) is not changed by input rate. To test this assumption in a clinical setting, a 25 micrograms/kg i.v. dose of doxacurium was administered either by bolus injection or 10-min infusion to 15 anesthetized patients. Neuro-muscular function was monitored using train-of-four stimulation of the ulnar nerve. For the short infusion dose, arterial concentrations were measured at I-min intervals during infusion and at frequent intervals thereafter. Following the iv bolus dose, the early PK profile of doxacurium was investigated by measuring doxacurium arterial concentrations every 10 sec during the first 2 min and at frequent intervals thereafter. PK-PD modeling was performed using nonparametric approach with and without including a finite receptor concentration (Rtot) in the effect compartment. Kinetic parameters were unchanged. For the bolus and the infusion, Ke0 values were 0.053 +/- 0.006 and 0.056 +/- 0.009 min-1, respectively. Using the Rtot model, corresponding Ke0 values were 0.148 +/- 0.016 and 0.150 +/- 0.024, respectively. The relatively faster Ke0 obtained with the Rtot model is compatible with the high potency of doxacurium. Our results show that PK-PD parameters derived with either a bolus or an infusion mode of administration are equally reliable.

Adult↗

PubMed1997

Pharmacokinetics of mivacurium isomers and their metabolites in healthy volunteers after intravenous bolus administration.

BACKGROUND: Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial-venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma. METHODS: Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high-performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters. RESULTS: Mean elimination half-lives of the trans-trans, cis-trans, and cis-cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml.min 1.kg-1. The volumes of distribution at steady state of the trans-trans, cis-trans, and cis-cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half-lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed. CONCLUSIONS: Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans-trans and cis-trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.

Adolescent↗

PubMed1996

Anticonvulsant pharmacodynamics and disposition of triazolam in rats.

Triazolam (TZ) is a triazolobenzodiazepine used in the treatment of insomnia that possesses significant anticonvulsant properties. Despite the widespread use of this drug, detailed pharmacokinetic-pharmacodynamic information is lacking, especially with respect to inhibition of seizure activity. TZ disposition has been described previously by methods with limited specificity, and the concentration-anticonvulsant effect relationship has not been characterized. The current studies were undertaken to examine TZ disposition with a specific HPLC method, and to evaluate the relationship between anticonvulsant effect and concentration in Sprague-Dawley rats. TZ pharmacokinetics were characterized after bolus or infusion administration; in a separate experiment, TZ pharmacodynamics were assessed with pentylenetetrazol-induced seizures. The systemic disposition of TZ could be described with a two-compartment model; systemic clearance ranged from 2.45 to 5.30 L/h/ kg, steady-state volume of distribution ranged from 2.10 to 4.02 L/kg, and mean residence time ranged from 47 to 65 min. The concentration-effect relationship was well described by a simple Emax model: Emax, expressed as the ratio of post-TZ to pre-TZ threshold convulsant doses of pentylenetetrazol, was 9.9 +/- 0.7, and the EC50 values were 10.0 +/- 4.6 ng/mL and 34.8 +/- 9.0 ng/g in serum and whole brain tissue, respectively. Under single-dose conditions, TZ is a very potent anticonvulsant in the rat pentylenetetrazol seizure model.

Animals↗

PubMed1996

Pharmacokinetic origin of carbamazepine-induced resistance to vecuronium neuromuscular blockade in anesthetized patients.

BACKGROUND: Patients receiving chronic carbamazepine therapy have shortened recovery times from a neuromuscular block induced by vecuronium. The current study investigates the pharmacokinetic or pharmacodynamic mechanisms responsible for this observation. METHODS: Pharmacokinetics and pharmacodynamics of 0.1 mg/kg intravenous bolus vecuronium in ten epileptic patients receiving chronic carbamazepine therapy were compared to that of ten control subjects. All patients were scheduled for neurosurgery while anesthetized with isoflurane and sufentanil. Arterial blood samples were collected for 6 h. Plasma vecuronium concentrations were measured by high-performance liquid chromatography coupled to electrochemical detection. The adductor pollicis force of contraction was recorded after supramaximal ulnar nerve stimulation. Plasma vecuronium concentrations were fitted to a two-compartment pharmacokinetic model, and the effect compartment equilibration rate constant was derived with a nonparametric link model. The effect compartment concentrations were fitted to a sigmoid Emax model. Results were compared using Student's t-test for independent samples. RESULTS: In the carbamazepine group, the mean recovery times to T(1) 25% were shorter (28.1 +/- 3.4 vs. 47.3 +/- 5.1 min in control subjects; P=0.007), and the T(1) 25% to T(1) 75% recovery index was decreased (7.6 +/- 1.2 vs. 21.9 +/- 6.8 min in control subjects; P=0.025). No changes in onset times were observed. Clearance was 9.0 +/- 1.2 ml x kg-1 x min-1 versus 3.8 +/- 0.3 in the control group (P=0.003), whereas no changes in volumes of distribution at steady-state were observed. Therefore, the mean residence time was halved (17.8 +/- 2.5 vs. 31.9 +/- 2.5 min in control subjects; P=0.001). No differences in the effect compartment equilibration rate constant, vecuronium effect compartment concentration present at a 50% block (EC50), or slope of the sigmoid between the two groups were found. CONCLUSIONS: The twofold increase in clearance provides evidence of a pharmacokinetic origin to the carbamazepine-vecuronium interaction; however, the possibility of a concurrent pharmacodynamic alteration cannot be assessed. Greater knowledge of protein drug binding needs to be acquired to give a meaningful interpretation to the similar EC50 values observed in the two groups.

Adult↗

PubMed1995

High-performance liquid chromatographic assays with fluorometric detection for mivacurium isomers and their metabolites in human plasma.

Two high-performance liquid chromatographic assays coupled with fluorometric detection have been developed for the determination of mivacurium isomers (trans-trans, cis-trans and cis-cis) and their monoester and alcohol metabolites in human plasma. A novel solid-phase extraction procedure allowed good recovery of the mivacurium isomers (mean 98%) and their monoester metabolites (mean 83%), whereas the alcohol metabolites were analyzed after direct precipitation of plasma proteins. For all analytes, these assays proved to be sensitive (LOQ 3.9-15.6 ng/ml), reproducible (C.V. < 15%) and accurate (> 94%) over the therapeutic range of concentrations of mivacurium and its metabolites. These two methods were applied successfully to a pharmacokinetic study of mivacurium after a bolus dose of 0.15 mg/kg in anesthetized patients.

Chromatography, High Pressure Liquid↗

PubMed1995

Pharmacokinetics and anticonvulsant effect of a new hypnotic, CL 284,846, in rats.

PURPOSE: CL 284,846 (CL846) is an investigational non-benzodiazepine agent with hypnotic, anxiolytic, myorelaxant and anticonvulsant properties. This study assessed the pharmacokinetics and anticonvulsant action of CL846 in female Sprague-Dawley rats. METHODS: CL846 pharmacokinetics were examined after either an iv bolus dose (2.5 mg/kg) or a 6-hr infusion (0.4 mg/kg/hr). CL846 pharmacodynamics were evaluated with a pentylenetetrazol (PTZ) infusion 5 min after a CL846 in bolus dose (0 to 10 mg/kg). CL846 and the derived metabolite CL 284,859 (CL859) concentrations in serum and brain tissue were determined by HPLC with fluorescence detection. RESULTS: Both the steady-state volume of distribution (1636 +/- 162 and 1804 +/- 293 ml/kg, after bolus and infusion administration, respectively) and systemic clearance (19.1 +/- 7.1 and 22.2 +/- 4.3 ml/min/kg for bolus and infusion administration, respectively) were high. No differences in pharmacokinetic parameters were noted between the two modes of administration. The relationship between anticonvulsant effect and brain/serum concentrations was well described by an Emax model. CL846 was as effective as triazolam in antagonizing PTZ-induced seizures. CONCLUSIONS: Under the conditions of the present study, CL846 pharmacokinetics were linear and stationary. Further evaluation of the anticonvulsant properties of CL846 is warranted, including the potential development of tolerance, which is well known for benzodiazepines.

Acetamides↗

PubMed1995

In vitro plasma protein binding of neuromuscular blocking agents in different subpopulations of patients.

In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate changes in their protein constituents. First, the relationship between the free fraction of atracurium and plasma lipoproteins levels in young volunteers (22-32 yr old, n = 6) and hyperlipidemic patients (44-68 yr old, n = 13) was studied, and second, the free fraction of atracurium, mivacurium, doxacurium, and vecuronium was determined in plasma of healthy young (27-47 yr old, n = 10), elderly (72-89 yr old, n = 11) and obese (21-57 yr old, n = 9, 200%-360% ideal body weight) patients scheduled for elective surgery. In hyperlipidemic patients, atracurium free fraction was significantly less than in young volunteers (40% +/- 5% vs 50% +/- 5%, mean +/- SD), and decreased as total cholesterol, low-density lipoprotein cholesterol and triglycerides increased (P < 0.05). In young individuals, NMBA free fraction was 25% +/- 5% for vecuronium, 58% +/- 8% for doxacurium, 52% +/- 6% for atracurium, and 72% +/- 3%, 70% +/- 3%, 70% +/- 4% for mivacurium trans-trans, cis-trans, and cis-cis isomers, respectively. Higher triglyceride concentrations in obese patients and lower high-density-lipoprotein cholesterol concentrations in both obese and elderly patients were observed when compared with young subjects. However, there was no significant difference in protein binding of NMBAs among these three groups. We conclude that, in otherwise healthy patients, age and weight are not likely to alter the free fraction of NMBAs.

Adult↗

PubMed1994

Determination of midazolam and two of its metabolites in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic assay coupled with UV detection (254 nm) has been developed for the determination of midazolam and two of its hydroxylated metabolites, 1-hydroxymidazolam (1-OH) and 4-hydroxymidazolam (4-OH), in human plasma. Following a novel solid-phase extraction procedure, midazolam and its metabolites are well recovered from plasma. The analytes were extracted with C1 cartridges and the extracts were evaporated to dryness. The dry residues were dissolved in 200 microliters of mobile phase [0.02 M ammonium phosphate monobasic buffer-methanol-acetonitrile (60:35:5, v/v) (300 ml), 600 microliters of 0.2 M tetrabutylammonium bromide solution, adjusted to a pH* (apparent pH) of 4.10]. The separation of the analytes was performed on a Spherisorb C8 column (10 cm x 4.6 mm I.D.) maintained at 30 degrees C. The mobile phase was pumped at a flow-rate of 1.5 ml/min. The method has a lower limit of quantitation of 15 ng/ml of plasma for midazolam and proved to be reproducible (inter-assay precision 5.4%) and accurate (94 +/- 5%) over the therapeutic range of concentrations.

Chromatography, High Pressure Liquid↗

PubMed1994

Bretylium decreases and verapamil increases defibrillation threshold in pigs.

BACKGROUND: Patients with ischemic heart disease may require antianginal and/or antiarrhythmic regimes. These patients may also be candidates for implantable defibrillators. The effects of antiarrhythmics, such as bretylium, or calcium antagonists, such as verapamil, nifedipine, or diltiazem on internal defibrillation efficacy have been inconsistent or are unknown. METHODS AND RESULTS: The effects of bretylium and verapamil on the energy requirements for ventricular defibrillation threshold (DFT) were determined in 92 open-chest anesthetized pigs. Triplicate DFTs were determined before and after intravenous administration of saline or one of four doses of verapamil, or saline or one of three doses of bretylium, in a balanced random order. Bretylium elicited a dose dependent reduction of DFT (F = 2.72 at 3 degrees and 36 degrees of freedom). DFT was significantly reduced with the highest dose of bretylium, (from 5.9 +/- 0.6 J to 4.7 +/- 0.6 J, mean +/- S.E.M.; P < 0.01). However, cardiac massage was sometimes needed at this dose due to low blood pressure immediately after defibrillation. In contrast, there was a positive correlation between DFT and serum verapamil concentration (r = 0.54, P < 0.001). The highest dose of verapamil significantly increased DFT (from 6.3 +/- 0.6 J to 8.2 +/- 1.1 J; P < 0.05), at a serum verapamil concentration of 86.6 +/- 6.8 ng/mL. CONCLUSIONS: These data indicate that bretylium decreases while verapamil increases the minimum energy requirement for internal defibrillation. Caution is warranted in patients who may be hemodynamically comprised and may be candidates for bretylium therapy or in patients who have marginal DFT value who might be candidates for verapamil therapy.

Animals↗

PubMed1993

Influence of aging on the pharmacokinetics and pharmacodynamics of doxacurium.

Doxacurium (30 micrograms/kg) pharmacokinetics and pharmacodynamics were evaluated in nine elderly (age range, 70 to 83 years) and nine young (age range, 19 to 39 years) patients under nitrous oxide-isoflurane anesthesia. The force of contraction of the adductor pollicis was monitored and plasma samples were collected for an 8-hour period. In the elderly group, doxacurium elimination half-life was prolonged (119.7 versus 75.9 minutes) and plasma clearance was significantly reduced (1.75 versus 2.54 ml/min/kg) without any change in volume of distribution. Onset (12.9 versus 8.9 minutes) and recovery times (113.4 versus 48.1 minutes) were longer in the elderly group. The equilibrium rate constant to the effect compartment (kco) was decreased in the elderly (0.039 versus 0.051 min-1), whereas the effect compartment concentration at 50% block was similar in both groups (44.7 versus 54.1 ng/ml). An age-related reduction in muscle blood flow may be responsible for the decrease in kco. The pharmacokinetic changes observed in the elderly are consistent with a decreased function in the organs of elimination.

Adult↗

PubMed1993

Importance of early blood sampling on vecuronium pharmacokinetic and pharmacodynamic parameters.

The effect of early blood sampling on the description of the vecuronium pharmacokinetic-pharmacodynamic relationship was studied following a bolus injection. Sample collection every 10 sec during the first 2 min showed a high concentration peak at 30 to 40 sec, accounting for an important proportion of the total area under the plasma concentration-time curve (AUC). Neglecting it, using only blood samples drawn at 1 and 2 min (limited sampling), led to a significant overestimation of noncompartmentally derived values of mean residence time, clearance, volume of distribution at steady-state and rate of transfer of vecuronium into the effect compartment. Compartmental pharmacokinetics could not be applied to concentration-time curves constructed with early samples, but limited sampling data were fitted to a 2-compartment model. Derived compartmental pharmacokinetic and pharmacokinetic-pharmacodynamic parameters were similar to those obtained noncompartmentally with complete sampling every 10 sec, because back-extrapolation to time zero contributed to the increase in the AUC. However, compartmental analysis does not provide an accurate description of concentration changes following injection.

Adult↗

PubMed1992

Simple, rapid and selective method using high-performance liquid chromatography for the determination of bretylium in plasma.

A high-performance liquid chromatographic method with ultraviolet detection has been developed for the determination of bretylium in plasma. Following a single-step solid-phase extraction procedure, bretylium is selectively isolated and well recovered from plasma. The assay sensitivity is 0.156 micrograms/ml from 250-microliters plasma samples and its linearity was assessed up to 40 micrograms/ml. The method is accurate (101.0 +/- 5.4%) and precise (maximum coefficient of variation of 8%). It provides a simple and time-saving alternative to existing methods and is particularly suitable for pharmacokinetic studies.

Animals↗

PubMed1992

High-performance liquid chromatographic determination of spironolactone and its metabolites in human biological fluids after solid-phase extraction.

A simple and sensitive high-performance liquid chromatographic procedure to determine spironolactone and its three major metabolites in biological specimens is described. The assay involves sequential extraction on C18 and CN solid phases, and subsequent separation on a reversed-phase column. In plasma samples, spironolactone and its metabolites were completely separated within 8 min using an isocratic mobile phase, while in urine samples a methanol gradient was necessary to achieve a good separation within 14 min. Recoveries for all analytes were greater than 80% in plasma and 72% in urine. Linear responses were observed for all compounds in the range 6.25-400 ng/ml for plasma and 31.25-2000 ng/ml for urine. The plasma and urine methods were precise (coefficient of variation from 0.8 to 12.5%) and accurate (-12.1% to 7.4% of the nominal values) for all compounds. The assay proved to be suitable for the pharmacokinetic study of spironolactone in healthy human subjects.

Chromatography, High Pressure Liquid↗

PubMed1992

High-performance liquid chromatography-electrochemical detection of vecuronium and its metabolites in human plasma.

A high-performance liquid chromatographic assay coupled with electrochemical detection has been developed for the determination of vecuronium and its three putative deacetylated metabolites in human plasma. A novel solid-phase extraction procedure allowed good recovery of both vecuronium and its metabolites, together with ease and speed of execution. This method was sensitive, reproducible and accurate over the therapeutic range of concentrations of vecuronium and its metabolites, and was applied successfully to a study of the pharmacokinetics of vecuronium in anaesthetized patients.

Chromatography, High Pressure Liquid↗

PubMed1992

Pharmacokinetics of sufentanil in normal children.

The pharmacokinetic variables of sufentanil were studied in 20 healthy children between two and eight years of age. The plasma concentrations of sufentanil were measured for up to 480 min after administration of a bolus of sufentanil, 1-3 micrograms.kg-1. The distribution half-life (t1/2 alpha) was 5.2 +/- 2.2 (mean +/- SD) min and the elimination half life (t1/2 beta) was 97.0 +/- 42.0 min. The volume of distribution at steady state (Vdss) was 2.9 +/- 0.6 L.kg-1 and the clearance was 30.5 +/- 8.8 ml.kg-1.min-1. The Vdss was one and a half times greater than that reported in adults when expressed as a function of body weight but similar to that of adults when expressed as a function of body surface area. According to our results, the clearance of sufentanil in normal children between two and eight years of age is twice as rapid as that described in adults and adolescents. A greater clearance of sufentanil in children suggests that they would require relatively greater maintenance doses than adults.

Anesthesia, General↗