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F Varin

Publications and source records attributed to F Varin.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1991

Isolation of 6-mercaptopurine in human plasma by aluminum ion complexation for high-performance liquid chromatographic analysis.

A sample preparation technique and a high-performance liquid chromatographic method for 6-mercaptopurine (6-MP) that is simple, sensitive and without interference from its metabolites is described. 6-Thioguanine (6-TG) is added as an internal standard to the plasma sample, which is then treated with an aqueous solution of aluminum perchlorate to denature the plasma proteins and form complexes with 6-TG, 6-MP and its major metabolite, 6-thiouric acid (6-TUA). These complexes coprecipitate with proteins on centrifugation. 6-MP and its analogues are then extracted from the precipitate with perchloric acid containing sodium hydrosulfite and the extract is chromatographed on an Ultrasphere ODS column eluted with 0.1 M phosphoric acid and 0.001 M dithiothreitol in deionized water. The eluate is monitored at 340 nm. No interfering peak was encountered in over 300 clinical plasma samples. 6-TUA was separated from 6-MP and was found to be present in much higher concentration than 6-MP itself throughout the sampling time (6 h) following oral administration of the drug.

Aluminum↗
PubMed1991

Residual curarization in the neonate after caesarean section.

The transplacental transfer and the neonatal effects of atracurium 0.3 mg.kg-1 (ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg.kg-1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 +/- 3% for atracurium and 12 +/- 5% for d-tubocurarine (P less than 0.05). The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (greater than or equal to 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P less than 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1991

Pharmacokinetics and pharmacodynamics of atracurium obtained with arterial and venous blood samples.

To determine the influence of sampling site on atracurium pharmacokinetic-pharmacodynamic relationships, blood was drawn simultaneously from the radial artery and peripheral vein during a 20-minute period after injection of atracurium, 0.2 mg/kg, in eight patients. Atracurium and laudanosine concentrations were measured by HPLC. Neuromuscular blockade was measured at the adductor pollicis, after stimulation of the ulnar nerve. Venous levels were lower than corresponding arterial values for up to 20 minutes, and this difference was marked for the early samples. Neuromuscular blockade was maximum after 5 to 7 minutes, much later than the peak venous concentration (1 to 3 minutes). Nonparametric analysis yielded (mean +/- SEM) a rate constant, concentration for 50% blockade, and slope of the effect-concentration relationship of 0.092 +/- 0.01 min-1, 379 +/- 27 ng/ml, and 7.3 +/- 1.67, respectively, when based on arterial samples. The values were statistically different (0.135 +/- 0.011 min-1, 235 +/- 42 ng/ml, and 3.41 +/- 0.37, respectively) when venous levels were used (p less than 0.05). It is concluded that forearm venous levels do not correspond to adductor pollicis neuromuscular blockade and the kinetics and kinetic-dynamic relationship for atracurium are heavily dependent on sampling site.

Adolescent↗
PubMed1991

Pharmacokinetics and pharmacodynamics of atracurium with and without previous suxamethonium administration.

Suxamethonium increases neuromuscular block produced by non-depolarizing agents administered subsequently. To determine if this effect has a pharmacokinetic or pharmacodynamic origin, 18 ASA physical status I or II adults received atracurium 0.2 mg kg-1, with (n = 10) or without (n = 8) previous injection of suxamethonium 1 mg kg-1, during a thiopentone-nitrous oxide-isoflurane (0.5% end-tidal) anaesthetic. Arterial blood samples were obtained and plasma atracurium concentration measured by HPLC. Train-of-four stimulation was applied to the ulnar nerve and the force of contraction of the adductor pollicis muscle was recorded. Mean (SEM) volume of distribution was slightly greater with previous suxamethonium (143 (13) ml kg-1) than without (109 (5) ml kg-1) (P less than 0.04). Mean elimination half-life was unaffected (20.3 (0.8) min and 20.4 (1.6) min, respectively). Neuromuscular block was more intense and recovery was slower with previous administration of suxamethonium. Atracurium concentration at 50% block (Cpss50) was 305 (30) ng ml-1 with and 454 (25) ng ml-1 without previous suxamethonium (P less than 0.01). It is concluded that suxamethonium may be associated with a slight increase in the volume of distribution of atracurium, but this effect is more than compensated by a decrease in atracurium concentration required for a given effect.

Adult↗
PubMed1991

Potentiation of atracurium neuromuscular blockade by enflurane: time-course of effect.

This study was designed to determine the time required for potentiation of atracurium neuromuscular blockade after the introduction of enflurane. Ten ASA physical status I and II adults anesthetized with thiopental, nitrous oxide, and alfentanil were given 0.4 mg/kg atracurium besylate. The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation of the ulnar nerve was recorded. When the first twitch (T1) of the train-of-four recovered to 10% of control, an atracurium infusion was started and adjusted to keep the level of blockade constant. After 15 min of stable blockade, 1.6%-1.7% end-tidal enflurane was started and maintained for up to 2 h. Venous blood samples were drawn and plasma atracurium concentrations were measured 15 min before and 0, 5, 10, 15, 30, 45, 60, 90, and 120 min after the introduction of enflurane. Atracurium plasma concentrations were 730 +/- 127 (SEM) ng/mL at time 0. During the first 30 min, no significant decrease in plasma levels occurred; but at 45 min, concentrations were only 67% +/- 8% of their initial value (P less than 0.01) and 48% +/- 2% at 120 min (P less than 0.01). This suggests that the interaction between enflurane and atracurium is time-dependent. Clinically, the interaction between atracurium and enflurane is negligible during procedures of less than 45 min.

Adult↗
PubMed1990

Determination of atracurium and laudanosine in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method coupled with fluorometric detection has been developed for the determination of atracurium and its major end-product laudanosine in human plasma. The method enables good separation of atracurium from its metabolites after direct precipitation of plasma proteins. The assay is sensitive, reproducible and linear for atracurium concentrations ranging from 31.25 to 8000 ng/ml. In a clinical setting, drugs commonly administered during anesthesia did not interfere with the assay. This method provides a simple and time-saving alternative to existing methods.

Atracurium↗
PubMed1990

Influence of food on the bioavailability of diltiazem and two of its metabolites following the administration of conventional tablets and slow-release capsules.

The influence of food on the bioavailability of a conventional tablet and of a slow-release capsule of diltiazem was investigated in two separate groups of 24 healthy volunteers in two open crossover studies. Diltiazem, as a conventional tablet (2 x 30 mg, first group) or as a slow-release capsule (120 mg SR, second group), was administered in a fasting condition and 30 min after a breakfast of 784 kcal (23 per cent proteins, 55 per cent lipids, and 22 per cent of carbohydrates). Multiple blood samples were withdrawn during the next 24 h and diltiazem, desmethyldiltiazem, and deacetyldiltiazem were assayed by HPLC. Neither the rate of absorption, assessed by the rate constant of absorption, the peak plasma concentration, and the time required to reach the peak, nor the amount of drug reaching the systemic circulation, assessed by the area under the plasma concentration time curve (AUC infinity) were influenced by food, and that independently of the formulation. Compared to the fasting experiment, food did not affect either the rate of formation or the AUC infinity of desmethyldiltiazem or deacetyldiltiazem. The results of the present study show that the relative bioavailability of the single dose of diltiazem administered as a slow-release capsule is significantly higher (69 per cent) than that estimated after the administration of diltiazem in a conventional tablet. It was concluded that food does not influence the bioavailability of diltiazem administered as a conventional tablet or as a slow-release formulation.

Administration, Oral↗
PubMed1990

Influence of extreme obesity on the body disposition and neuromuscular blocking effect of atracurium.

The pharmacokinetics and pharmacodynamics of atracurium, a nondepolarizing neuromuscular blocking agent, were compared between morbidly obese patients and nonobese patients. Atracurium besylate (0.2 mg/kg) was administered intravenously as a bolus to patients who had received anesthesia. The force of contraction of the adductor pollicis was measured and plasma samples were collected for a 2-hour period. The concentrations of atracurium and its major end product, laudanosine, were determined by use of a chromatographic method. The pharmacokinetic-pharmacodynamic relationship was characterized by use of several models. No difference was observed between obese patients and nonobese patients in atracurium elimination half-life (19.8 +/- 0.7 versus 19.7 +/- 0.7 minutes), volume of distribution at steady state (8.6 +/- 0.7 versus 8.5 +/- 0.7 L), and total clearance (444 +/- 29 versus 404 +/- 25 ml/min). However, if values were expressed on a total body weight basis, there was a difference between obese and nonobese patients in the volume of distribution at steady state (0.067 versus 0.141 L/kg) and total clearance (3.5 +/- 0.2 versus 6.6 +/- 0.5 ml/min/kg). Although atracurium concentrations were consistently higher in obese patients than in nonobese patients, there was no difference in the time of recovery from neuromuscular blockade between the two groups. Consequently, the median effective concentration was higher in obese than in nonobese patients (470 +/- 46 versus 312 +/- 33 ng/ml).

Adult↗
PubMed1989

Determination of opiates and other basic drugs by high-performance liquid chromatography with electrochemical detection.

A procedure is described for the extraction and determination of morphine (M), hydromorphone (HM), codeine (C) and metoclopramide (MCP) present in human plasma. The drugs are separated by reversed-phase liquid chromatography and detected amperometrically at a glassy carbon electrode. The method provides high sensitivity and selectivity and has been used successfully in bioavailability studies.

Biological Availability↗
PubMed1987

Clinical pharmacology of carvedilol in normal volunteers.

The mechanism of the vasodilatory action of carvedilol (BM 14190), a new antihypertensive agent, was investigated in normal volunteers. Intra-arterial blood pressure and ECG were monitored continuously. Carvedilol (1 mg/min for 15 minutes) produced a rapid reduction in blood pressure and a transient increase in heart rate. At the end of infusion, systolic and diastolic blood pressure were reduced by 23% (-32.3 mm Hg) and 18% (-13.6 mm Hg), respectively, whereas heart rate was not different from baseline. At the doses used, the hypotensive effect of carvedilol was greater than that of labetalol (36 and 72 mg in 15 minutes). Carvedilol and labetalol antagonized isoproterenol-induced hypotension and tachycardia, at serum levels greater than or equal to 8 and 20 mg/ml, respectively. Both drugs antagonized phenylephrine pressor effects. A similar degree of inhibition (25% of control) of pressor effects was observed for carvedilol and labetalol when their respective serum concentrations were 23 ng/ml and 80 ng/ml. Neither carvedilol nor labetalol had any effect on AII pressor responses. Carvedilol serum levels as high as 150 ng/ml failed to inhibit AII-induced pressor responses. Our results suggest that at the doses used in this study, carvedilol has both alpha 1-and nonselective beta-receptor blocking properties. Moreover, carvedilol is approximately three to five times more potent than labetalol in blocking alpha 1-and beta-receptors and in reducing blood pressure.

Adult↗