Plasma Alfentanil Concentrations Research Articles

Application of physiologic models to predict the influence of changes in body composition and blood flows on the pharmacokinetics of fentanyl and alfentanil in patients.

The influence of changes in the physiologic state of a patient on the disposition of fentanyl and alfentanil is poorly understood. The aims of this study were to determine whether physiologic pharmacokinetic models for fentanyl and alfentanil, based on data from rats, could predict plasma concentrations of these opioids in humans and to determine how changes in physiology would influence the predictions of their disposition. The predictions of the models were tested against plasma concentration data from published pharmacokinetic studies. The influences of changes in body composition, cardiac output, and regional blood flows on the disposition of the opioids were simulated. The models could predict independently measured plasma concentrations of the opioids after short infusions in humans. Simulations then predicted that differences in body composition between men and women would have little influence on the pharmacokinetics of the opioids. Changes in cardiac output would affect drug redistribution, and consequently the early decay of the plasma concentrations, but not markedly influence rates of elimination. Further, the clearance of the opioids would decrease and their volumes of distribution increase with the age of the patient, but this would only marginally affect the early disposition of the drugs. Even large fluctuations in peripheral or hepatic blood flows would have modest effects on arterial plasma concentrations of the opioids, and sudden "postoperative" increases in peripheral blood flows would cause minor secondary plasma concentration peaks. The ability of the physiologic models to predict plasma concentrations of fentanyl and alfentanil in humans was confirmed. When changes in physiologic condition were simulated, effects on the pharmacokinetics of the opioids with possible implications for dosing were obtained only if cardiac output was varied over a wide range.

Effect of alfentanil on the minimum alveolar concentration of isoflurane in cats

SUMMARY Objective To evaluate effect of incremental doses of alfentanil on isoflurane minimum alveolar concentration (MAC) in cats to determine whether alfentanil reduces isoflurane MAC and, if so, maximal isoflurane MAC reduction. Animals 6 healthy spayed female cats. Procedure Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood for measurement of gas tensions, pH, and plasma alfentanil concentration and to measure arterial blood pressure. Isoflurane MAC was determined in triplicate, and alfentanil was administered IV, using a computer-driven syringe pump to achieve estimated plasma alfentanil concentrations of 50, 100, 250, 500, 750, and 1,000 ng/ml; isoflurane MAC was determined at each alfentanil concentration. Cats were allowed to recover, and the process was graded as poor, good, or excellent. Results Alfentanil had a significant dose effect on isoflurane MAC reduction. Significant regression was found for normalized isoflurane MAC versus estimated plasma alfentanil concentration. A quadratic term was necessary to fit the model and, using this curve, MAC reduction (35.0 ± 6.6%) was estimated to be maximal at a plasma alfentanil concentration of 500 ng/ml. Significant differences were evident in rectal temperature, bicarbonate concentration, base deficit, arterial carbon dioxide and oxygen tensions, and arterial pH between isoflurane alone and some plasma alfentanil concentration and the corresponding reduction in isoflurane concentration. Conclusions Infusion of alfentanil resulted in maximal MAC reduction midway between that reported for horses and dogs. At such plasma alfentanil concentration, adverse effects were minimal, but included increase in rectal temperature, metabolic acidosis, and decrease in Pao2. Provided cats were not handled during the recovery period, recovery was smooth and quiet. Clinical Relevance Infusion of alfentanil decreases the need for potent inhalant anesthetics in cats and could potentially be a clinically useful anesthetic regimen in sick cats. (Am J Vet Res 1997;58:1274–1279)

Effect of Midazolam on Development of Acute Tolerance to Alfentanil

This study in rats was performed to explore whether the inhibitory effect of midazolam on the development of acute tolerance to the analgesic effect of alfentanil is due to pharmacokinetic mechanisms. Analgesia was determined with tail-compression and hot-plate tests. Alfentanil and midazolam concentrations in plasma and the brain were measured using a radioimmunoassay and chromatographic technique, respectively. After the 4-h period of alfentanil administration (155 microg x kg(-1) x h(-1) after a 50-microg/kg bolus), when acute tolerance had already developed, midazolam (2-mg/kg bolus) enhanced the alfentanil-induced analgesia by 120% (P < 0.001) with the tail-compression test and 76% (P < 0.01) with the hot-plate test. At the height of midazolam-induced enhancement of the analgesic effect of alfentanil, the measurements of the alfentanil and midazolam plasma and brain concentrations did not demonstrate any significant changes in the drugs' concentrations. The results confirm that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil and indicate that this interaction is not pharmacokinetic.

Assessment of cytochrome P450 3A4 activity during the menstrual cycle using alfentanil as a noninvasive probe.

Gender-dependent differences in cytochrome P450 activity, drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is responsible for metabolizing a vast and diverse assortment of therapeutic agents, including opioids, benzodiazepines, and local anesthetics. P450, 3A4 activity is higher in women, influenced by steroid hormone levels, and is speculated to vary during the menstrual cycle. This investigation tested the hypothesis that P450 3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as a metabolic probe for P450 3A4 activity. Alfentanil (20 micrograms/kg bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age, 26 +/- 5 yr) with normal menstrual cycles on three separate occasions during the same menstrual cycle: days 2 (menstrual phase), 13 (estrogen peak), and 21 (progesterone peak). Venous plasma alfentanil concentrations were determined by gas chromatography-mass spectrometry. Alfentanil clearance was determined by noncompartmental methods and by a three-compartment model with both pooled population and two-stage analysis. There was no significant difference in any measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD) were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on days 2, 13, and 21 of the menstrual cycle. Alfentanil clearances were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances do not contribute to interindividual variability in alfentanil disposition in women. If other P450 3A4 substrates are comparable, then menstrual cycle variability in their metabolism may not be a consideration in dosing or in the design of pharmacokinetic investigations.

Clonidine for Major Vascular Surgery in Hypertensive Patients

The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable.Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micro gram/kg per os 120 min before induction of anesthesia and 3 micro gram/kg intravenously (IV) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micro gram/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 micro gram centered dot kg-1 centered dot min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures. (Anesth Analg 1996;83:687-95)

Time course characteristics of acute tolerance development to continuously infused alfentanil in rats.

The time course of the development of acute tolerance to alfentanil was characterized in rat experiments using various algorithms of continuous infusion of the drug. To maintain analgesia at a constant level (tail compression test), alfentanil use was steadily increased: Time to 50% increase in alfentanil use was 255 +/- 98 min with analgesia maintained at a level of 50% increase in the pressure threshold, and 203 +/- 116 min with analgesia maintained at a level of 200% increase. With the use of the alfentanil infusion regimen designed to rapidly achieve and maintain the constant alfentanil plasma concentration (120 ng/mL), the rate of development of acute tolerance, measured in terms of time to 50% recovery during continuing infusion, was 81 +/- 26 min with the compression test and 88 +/- 38 min with the hot-plate test, but 374 +/- 46 min with the rotarod test (P < 0.0001). Thus we demonstrated rapid development of acute tolerance to continuously infused alfentanil with different methods of tolerance assessment. The results also indicate that the time course of tolerance development does not depend on the type of noxious stimulation (mechanical versus thermal) if the response is organized predominantly supraspinally, and that acute tolerance to the direct effect of alfentanil on motor functions does not mask the rapid development of tolerance to its analgesic effect.

Influence of Escherichia coli Endotoxin on the Pharmacokinetics and Respiratory Depressant Effect of Alfentanil in Rabbits

Postoperative fever occurs in many surgical patients, due to release of pyrogens into the circulation. Pyrogens and fever may influence the pharmacokinetics and effects of drugs. The aim of this study was to investigate the interactions of a pyrogen with the opioid analgesic alfentanil in an animal model. Alfentanil was infused over 10min into 17 conscious rabbits and over 120min in another 12 animals. Some of them had been randomized to pretreatment with Escherichia coli endotoxin. Arterial plasma concentrations of alfentanil were determined repeatedly, and arterial blood gas values were recorded. Endotoxin antagonized the respiratory depressant effect of the 10-min infusion of alfentanil by increasing drug distribution clearance during the infusion. In addition, endotoxin raised the total volume of distribution of alfentanil from 0.70 to 1.4 L/kg. Plasma protein binding and elimination clearance were not affected. The increase in volume of distribution and the lack of effect of endotoxin on elimination clearance were confirmed in the 120-min infusion experiments. Apparent concentration–effect relationships for the actions of alfentanil on arterial CO2, O2, and pH were not influenced by the endotoxin. Circulating pyrogens can thus influence the pharmacokinetics and, indirectly, the effects of alfentanil.

Effect of the addition of alfentanil to lignocaine during axillary brachial plexus anaesthesia

Peripheral administration of opioids has been suggested as a means of improving regional block. We studied 60 patients receiving axillary brachial plexus anaesthesia, allocated randomly to receive either normal saline 10 ml or normal saline 10 ml with alfentanil 10 micrograms/kg body weight through an axillary cannula. All patients received 1.5% lignocaine at a dose of 7 mg/kg body weight with adrenaline 1 in 200,000. The incidence of satisfactory block was similar in both groups. Although the percentage of patients with complete anaesthesia in the median nerve distribution was greater in the alfentanil group, there was no significant difference in any other distribution. The time to return of sensation and motor function was prolonged significantly in the alfentanil group (P < 0.05). After return of normal sensation, there was no significant difference between groups in postoperative analgesia. In a second part of the study, there was no significant increase in plasma concentrations of alfentanil in 10 patients given lignocaine and alfentanil, as outlined above. These observations suggest that alfentanil may have a peripheral local anaesthetic action.

A pharmacokinetic approach to resolving spinal and systemic contributions to epidural alfentanil analgesia and side-effects

A pilot study was conducted in 7 normal volunteers to demonstrate the feasibility of employing pharmacokinetic tailoring to achieve matching plasma opioid concentration-time curves after epidural (e.p.) and intravenous (i.v.) alfentanil administration. Each subject participated in 1 pretest and 2 test sessions. Our pain model was cutaneous electrical stimulation of the finger and toe, adjusted to produce a baseline pain report of 5 (strong pain on a 0–5 scale). On test day 1, subjects received e.p. alfentanil (750 μg) and an i.v. saline infusion. Serial measurements of analgesia, end tidal CO 2, pupil size, subjective side effects, and plasma alfentanil concentrations were conducted before and at various time intervals over a 4-h period after alfentanil administration. On test day 2, subjects received e.p. saline and a pharmacokinetically tailored i.v. infusion (using individual pharmacokinetics determined on the pretest day) designed to achieve a plasma concentration-time profile identical to that observed on the epidural day. The same battery of effect measurements was administered as on the 1st test day. Plasma alfentanil was measured to verify the accuracy of the tailored infusion. Plasma alfentanil concentration profiles were nearly identical on both test days. Peak plasma alfentanil concentrations were near the reported minimum effective analgesic concentration (MEAC). Overall, analgesia was slightly greater with e.p. administration. Onset of pain relief was rapid, and duration was approximately 1.5 h with e.p. and 1 h with i.v. alfentanil. There were no differences in pupil size, ETCO 2, or subjective side effects between e.p. versus i.v. administration. We concluded that a 750 μg dose of e.p. alfentanil produces plasma drug concentrations within the analgesic range and that systemic redistribution from the epidural space appears to account for most, but not all, of the analgesia. Side effects appear to be due to systemic absorption of the opioid. There may be little clinical benefit to e.p. administration at doses which result in plasma alfentanil concentrations near the MEAC.

Alfentanil slightly increases the sweating threshold and markedly reduces the vasoconstriction and shivering thresholds.

Hypothermia is common in surgical patients and victims of major trauma; it also results from environmental exposure and drug abuse. In most cases, hypothermia results largely from drug-induced inhibition of normal thermoregulatory control. Although opioids are given to a variety of patients, the thermoregulatory effects of opioids in humans remain unknown. Accordingly, the hypothesis that opioid administration impairs thermoregulatory control was tested. Eight volunteers were studied, each on 3 days: (1) a target total plasma alfentanil concentration of 100 ng/ml, (2) control (no drug), and (3) a target alfentanil concentration of 300 ng/ml. Each day, skin and core temperatures were increased sufficiently to provoke sweating. Temperatures subsequently were reduced to elicit peripheral vasoconstriction and shivering. Mathematical compensations were made for changes in skin temperature using the established linear cutaneous contributions to control of sweating (10%) and to vasoconstriction and shivering (20%). From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C) and unbound plasma alfentanil concentrations, the individual concentration-response relationship was determined. The concentration-response relationship for all the volunteers was determined similarly using total alfentanil concentrations. In terms of unbound concentration, alfentanil increased the sweating threshold (slope = 0.021 +/- 0.016 degrees C.ng-1.ml; r2 = 0.92 +/- 0.06). Alfentanil also significantly decreased the vasoconstriction (slope = -0.075 +/- 0.067 degrees C.ng-1.ml; r2 = 0.92 +/- 0.07) and shivering thresholds (slope = -0.063 +/- -0.037 degrees C.ng-1.ml; r2 = 0.98 +/- 0.04). In terms of total alfentanil concentration (degrees C.ng-1.ml), the sweating threshold increased according to the equation: threshold (degrees C) = 0.0014[alfentanil] + 37.2 (r2 = 0.33). In contrast, alfentanil produced a linear decrease in the core temperature, triggering vasoconstriction: threshold (degrees C) = -0.0049[alfentanil] + 36.7 (r2 = 0.64). Similarly, alfentanil linearly decreased the shivering threshold: threshold (degrees C) = -0.0057[alfentanil] + 35.9 (r2 = 0.70). The observed pattern of thermoregulatory impairment is similar to that produced by most general anesthetics: a slight increase in the sweating threshold and a substantial, linear decrease in the vasoconstriction and shivering thresholds.

Quantifying Anesthetic Drug Interaction

Quantifying Anesthetic Drug Interaction

Pharmacokinetics of intranasal alfentanil

Study Objective: To determine the pharmacokinetics of intranasal and intravenous (IV) administrations of alfentanil in 10 healthy volunteers. Design: Randomized, prospective, double-blind, placebo-controlled, cross-over trial with at least one week between the two modes of administration. Setting: Healthy volunteers at a university medical center. Subjects: 10 healthy, nondrug-dependent volunteers. Interventions: Alfentanil 0.54 mg was administered either intranasally [with 12 ml of sodium chloride (NaCl) 0.9% IV] or IV (with 12 sprays of NaCl 0.9% intranasally). Each subject was assigned once to the intranasal and once to the IV group. To guarantee a complete elimination of alfentanil, there was a time period of at least one week between the different modes of administration. Measurements and Main Results: Venous blood was sampled from a cubital vein at 3, 6, 9, 12, 15, 20, 30, 60, and 120 minutes after administration. Alfentanil plasma concentrations were determined by radioimmunoassay. Maximal plasma concentrations were 20.1 ng/ml ± 7.3 ng/ml after 9 minutes in the intranasal group. At this measurement point, the intranasal alfentanil concentrations were 64.7% (18.7 ng/ml ± 6.8 ng/ml) of the IV concentrations (28.9 ng/ml ± 7.9 ng/ml). The calculated bio-availability after intranasal administration was 64.96% ± 26.3%. Conclusions: This pharmacokinetic study demonstrates a rapid rise in plasma concentrations, as well as a high bioavailability, following the intranasal administration of alfentanil.

Pharmacokinetics of Alfentanil in Patients Treated with either Cimetidine or Ranitidine

KIENLEN, J.; LEVRON, J. -C.; AUBAS, S.; ROUSTAN, J. -P.; CAILAR, J. DU Author Information

Plasma concentrations of alfentanil following epidural administration.

The plasma concentration-time profile of alfentanil following epidural administration was determined in eight patients undergoing lower abdominal surgery under nitrous oxide (66%)-oxygen (33%)-halothane (0.3%) anaesthesia, supplemented with intravenous sufentanil. Alfentanil (1 mg) was administered epidurally before induction of general anaesthesia. Blood samples for the determination of plasma alfentanil concentrations by capillary gas chromatography were collected at intervals until 12 h after the epidural injection. Peak plasma concentrations [mean (SD)] were 9.7 (2.3)ng.ml-1, and were attained in a median (range) time of 90 (30-120) min. The results suggest that alfentanil is slowly absorbed from the epidural space into the general circulation.

Total intravenous anesthesia using propofol and alfentanil for coronary artery bypass surgery

Total intravenous anesthesia (TIVA) using alfentanil and propofol was used in 10 patients undergoing coronary artery bypass grafting. In an attempt to diminish unwanted side effects, lower doses were chosen than if either drug had been used alone. Anesthesia was induced with alfentanil, 75 μg/kg, followed by a sleep dose of propofol (mean dose 0.5 mg/kg). Maintenance in the precardiopulmonary bypass (CPB) period was achieved by infusions of propofol (6 mg/kg/h) and alfentanil (100 μg/kg/h). These were decreased by two thirds on commencement of CPB, and increased to half the initial rate on rewarming to 32°C. Additional boluses of alfentanil were used to control breakthrough hypertension. The mean arterial pressure (MAP) and left ventricular stroke work index (LVSWI) fell significantly on induction. MAP but not LVSWI returned to baseline levels at skin incision. The cardiac index (Cl) was maintained. A degree of myocardial depression was suggested by a fall in LVSWI despite maintaining preload, and by the failure of CI to increase in the presence of a reduced SVR. Anesthesia was satisfactory in all but one patient who developed break-through hypertension on sternotomy with transient ST segment depression, and awareness after CPB despite a plasma alfentanil concentration of 450 ng/mL. Mean time to wakening was 55 minutes. The study indicated that TIVA using propofol and alfentanil in the dosages described provides satisfactory basal anesthesia for coronary artery bypass surgery in patients with good left ventricular function, but requires additional pharmacologic manipulation, particularly with boluses of alfentanil, to control breakthrough hypertension.

Effect of xylazine and ketamine on the pharmacokinetics of alfentanil during halothane anaesthesia

We measured plasma concentrations of alfentanil in two horses after three different randomly ordered treatments. Each horse received halothane in oxygen by mask followed by a bolus dose of alfentanil 60 micrograms kg-1 i.v., halothane in oxygen by mask followed by an i.v. alfentanil infusion for 120 min and xylazine and ketamine followed by halothane and a bolus dose of alfentanil 60 micrograms kg-1 i.v. Halothane was maintained at 1.05-1.07% end-tidal concentration with a PaCO2 of 6-7.3 kPa. The plasma concentration-time curves were similar after bolus and infusion doses of alfentanil with halothane and could be fitted to a two-compartment open model. A plateau was noted in the plasma concentration-time curve in the presence of xylazine-ketamine which could not be modelled adequately, but suggested a three-compartment open model with an additional input component.

Pharmacokinetics of Alfentanil in Patients Treated with Either Cimetidine or Ranitidine

The pharmacokinetics of alfentanil were studied after single dose intravenous administration of 125 μg/kg to 19 intensive care unit patients who were divided into 3 groups. Group I was given oral antacid, and groups II and III were given, respectively, cimetidine 1200 mg/day IV and ranitidine 300 mg/day IV for 48 hours before administration of alfentanil. Alfentanil plasma concentrations were determined over the 8 hours following drug administration using a radio-immunoassay. Pharmacokinetic parameters were calculated using a noncompartmental analysis. In group II, alfentanil plasma concentrations were significantly higher than in the other groups. In addition, significant changes involving the elimination half-life (142.3 ± 35 vs 81.14 ± 11 and 88.1 ± 33 minutes), total clearance (1.27 ± 0.5 vs 3.56 ± 1.17 and 2.74 ± 1 ml/kg/min) and total volume of distribution related to the pseudo distribution phase (226 ± 73 vs 336 ± 76 and 271 ± 61 ml/kg) were found in group II vs groups I and III. These results suggest that pretreatment with cimetidine alters alfentanil pharmacokinetics after single dose administration. In contrast, ranitidine does not appear to have a significant effect.

Cognitive and motor function impairments during continuous opioid analgesic infusions

AbstractThis research was supported in part by grants from National Cancer Institute (CA 38552) and assistance from Janssen Research Foundation.Morphine and other opioid analgesics may interfere with normal cognition and motor function during long‐term treatment of cancer‐related pain. In this study, we used individually tailored steady‐state drug infusions to control plasma concentrations of morphine and alfentanil and measured the extent of cognitive and motor impairments produced by each drug in healthy volunteers. The tailored infusions allowed evaluation of cognitive and motor effects at three sequential, steady plasma concentrations of each opioid. During continuous infusion, both drugs caused significant, plasma concentration‐related impairments of ability to process serially‐presented information and of fine motor control at plasma drug concentrations within the usual therapeutic range. We found significant relationships between cognitive and motor function decrements and plasma opioid concentration with both morphine and alfentanil. We conclude that magnitudes of cognitive and motor function impairments are equivalent for these two mu receptor selective agonists at equianalgesic plasma concentrations.

Computer-controlled infusion of alfentanil for postoperative analgesia. A pharmacokinetic and pharmacodynamic evaluation.

Although computer-controlled infusion (CCI) of alfentanil has been shown to be effective intraoperatively, this technique has not been validated for postoperative use. Therefore, the authors examined the efficacy of this technique in providing postoperative pain relief. The study comprised both a validation of published pharmacokinetic data sets and the definition of the minimum effective analgesic concentrations after major orthopedic surgery. The bias and inaccuracy of the implemented pharmacokinetic data set were examined, in 20 patients who had undergone major orthopedic surgery, by determination of the median performance error (MDPE) and median absolute performance error (MDAPE). The performance of two other published pharmacokinetic data sets was also examined by simulating the plasma concentrations that would have been predicted, had these data sets been implemented. The minimum effective analgesic concentrations (MEAC) were determined at the following time points: at the onset of pain, at 9:00 PM on the day of surgery, and at 9:00 AM and 9:00 PM on the first postoperative day. Measured plasma concentration-time profiles generally were parallel to the target concentration-time profiles. The MDPE and MDAPE obtained were 12% and 28%, respectively. The MEACs ranged from < 1 to 175 ng/ml and showed substantial interindividual variability. The median MEACs at the four study times were 59, 52, 65, and 43 ng/ml. The MEAC at 9:00 PM on the first postoperative day was significantly lower than those at the other study times (P < 0.05). Computer-controlled infusion of alfentanil provides adequate postoperative analgesia. The study demonstrated that pharmacokinetic data sets that are useful for intraoperative CCI of alfentanil are equally valid in the postoperative phase. Although required plasma concentrations of alfentanil are reasonably stable in time, interindividual variations are large, necessitating individual titration.

Pharmacodynamics of alfentanil as a supplement to propofol or nitrous oxide for lower abdominal surgery in female patients.

Although propofol and alfentanil are given in combination in clinical practice, the pharmacodynamic interaction between these drugs has not been described. The pharmacodynamics of alfentanil when given as a supplement to propofol were studied in 10 ASA physical status 1 female patients (group P) undergoing lower abdominal surgery and compared to the pharmacodynamics of alfentanil when given as a supplement to nitrous oxide (group N, n = 10). Anesthesia was induced by either computer-controlled infusion of propofol and alfentanil at target concentrations of 3 micrograms/ml and 100 ng/ml (group P) or computer-controlled infusion of 400 ng/ml alfentanil as a supplement to nitrous oxide and oxygen (ratio 2:1; group N). The target concentration of alfentanil was varied to patient responses, and the nitrous oxide and propofol concentrations were maintained constant. A sigmoid Emax model was fitted to response/no response data versus plasma alfentanil concentrations at intubation, skin incision, and the opening of the peritoneum in both groups and for the intraabdominal part of surgery in the individual patients. In addition, the speed of recovery in both groups was determined by a deletion-of-p's test. The EC50 (the concentration at which, with a 50% probability, the patients did not respond to the surgical stimuli) of alfentanil during propofol anesthesia was 92 ng/ml for intubation, 55 ng/ml for skin incision, 84 ng/ml for the opening of the peritoneum, and 66 +/- 38 ng/ml (mean +/- SD) for the intraabdominal part of surgery. The corresponding values during nitrous oxide anesthesia were significantly higher: 429 ng/ml for intubation, 101 ng/ml for skin incision, and 206 +/- 65 ng/ml for the intraabdominal part of surgery (P < 0.001). The speed of recovery was similar in both groups. The alfentanil requirements in ASA physical status 1 female patients undergoing lower abdominal surgery are less when given as a supplement to propofol (4 micrograms/ml) compared to 66% N2O.