Alfentanil Hydrochloride

Pharmacopoeias. In Eur. (see p. vii) and US.
Ph.D. Eur. 8: (Alfentanil Hydrochloride) . A white or almost white powder. Freely soluble in water, in alcohol, and in methyl alcohol. Protect from light.
USP 36: (Alfentanil Hydrochloride) . A white to almost white powder. Soluble in water; freely soluble in alcohol, in chloroform, and in methyl alcohol; sparingly soluble in acetone. Store in airtight containers.

Uses and Administration
Alfentanil is a short-acting opioid analgesic related to fentanyl
Alfentanil is used in surgical procedures as an analgesic and adjunct to general anesthetics or as a primary anesthetic. It is also used as an analgesic and respiratory depressant in the management of mechanically ventilated patients under intensive care.
Alfentanil is given intravenously as the hydrochloride although doses are expressed in terms of the base. Alfentanil hydrochloride 108.8 micrograms is equivalent to about 100 micrograms of alfentanil. A peak effect may be seen within 1.5 to 2 minutes of an injection and analgesia can be expected to last for up to 10 minutes; dose supplements are therefore required if it is to be used for more prolonged surgical procedures. It may be given by continuous intravenous infusion in ventilated patients.
The dosage of alfentanil used depends on whether the patient has spontaneous respiration or assisted ventilation and on the expected duration of anesthesia. Doses are adjusted according to the needs of the patient. Children may require higher or more frequent doses than adults, whereas the elderly or debilitated patients may require lower or less frequent doses. Obese patients may require doses based on their ideal (lean) body-weight.
When used as an adjunct in the maintenance of general anesthesia the initial licensed dose in the UK is as follows:
• in patients with spontaneous respiration, up to 500 micrograms may be given slowly over about 30 seconds with supplementary doses of 250 micrograms
• ventilated patients may be given 30 to 50 micrograms/kg with supplements of 15 micrograms/kg. When given by infusion to ventilated patients there is an initial loading dose of 50 to 100 micrograms/kg given as a bolus or by infusion over I0 minutes, followed by infusion at a rate of 0.5 to I microgram/kg per minute
Typical doses that have been used in the USA are as follows:
• for short surgical procedures of less than 1 hour in patients with spontaneous respiration or assisted ventilation, the dose is 8 to 20 micrograms/kg; this may be followed by additional doses of 3 to 5 micrograms/kg every 5 to 20 minutes or an infusion of 0.5 to 1 microgram/kg per minute. Alternatively patients with assisted or controlled ventilation may be given an initial dose of 20 to 50 micrograms/kg, followed by supplementary doses of 5 to 15 micrograms/kg every 5 to 20 minutes
• in general surgical procedures in patients with assisted or controlled ventilation, an initial dose of 50 to 75 micrograms/kg may be followed by an infusion of 0.5 to 3 micrograms/kg per minute. If alfentanil has been given in anesthetic doses (see below) for the induction of anaesthesia, infusion rates may need to be reduced by 30 to 50% during the first hour of maintenance Maintenance infusions of alfentanil should be stopped 10 to 30 minutes before the anticipated end of surgery. The dose for the induction of anesthesia in patients with assisted ventilation undergoing procedures of at least 45 minutes is 130 to 245 micrograms/kg, followed by an inhalation anesthetic or maintenance doses of alfentanil of 0.5 to 1.5 micrograms/kg per minute.
For details of doses in children, see below.
In the UK, ventilated patients in intensive care may be given alfentanil initially at an infusion rate of 2 mg/hour or a loading dose of 5 mg may be given in divided doses over 10 minutes or more slowly if hypotension or bradycardia occur. After that a suitable rate of infusion should be determined for each patient (rates of 0.5 to 10 mg/hour have been used); patients should be carefully monitored and the duration of treatment should not generally exceed 4 days. During continuous infusion additional bolus injections of 0.5 to I mg may be given if required to provide analgesia for short painful procedures that may be carried out in intensive care.
Alfentanil is also used as an analgesic in patients with spontaneous respiration receiving monitored anesthesia care; in the USA, an initial dose of 3 to 8 micrograms/kg may be followed by supplementary doses of 3 to 5 micrograms/kg every 5 to 20 minutes or an infusion of 0.25 to I microgram/kg per minute.

Administration
Alfentanil is usually given by intravenous injection or infusion, but has also been given intramuscularly, 1.2 intrathecally, 3 or epidurally
I. Arendt-Nielsen L, et al. Analgesic efficacy of alfentanil. B r J Anaesth 1 990: 65: 164-8.
2. Virkkila M, et al. Pharmacokinetics and effects of i.m. alfentanil as pcemC<Jketion for day-case ophthalmic surgery in elderly patients. Br.J 1993; 71: 507-l l .
3. Hughes DA, Hill DA. Intrathecal alfentanil with and without bupivacaine for analgesia in labor. Anesthesia 2000; 55: 1 1 1 6-21.

Administration in children
In the UK, the BNFC recommends the use of intravenous alfentanil in ventilated children as an analgesic and adjunct to general anesthetics; the following doses, given according to age, are suggested: for short procedures in patients vvith assisted ventilation by injection over 30 seconds
• neonates, 5 to 20 micrograms/kg initially, followed by supplementary doses of up to I 0 micrograms/kg
• I month to 18 years. 10 to 20 micrograms/kg initially, followed by supplementary doses of up to 10 micrograms/kg for longer procedures in patients with assisted ventilation by infusion
• neonates, 10 to 50 micrograms/kg over 10 minutes initially, followed by 0.5 to I microgram/kg per minute
• I month to 18 years, 50 to 100 micrograms/kg over 10
minutes initially, followed by 0.5 to 2 micrograms/kg per minute (or 1 microgram/kg per minute when used with an intravenous anesthetic) Similar doses are licensed in the UK for use in children with spontaneous respiration or assisted ventilation although age ranges are not specified; equipment for assisted ventilation should be available for use, even for short procedures in those who are breathing spontaneously.

Anesthesia
Alfentanil, like fentanyl, appears to produce fewer circulatory changes than morphine and may be preferred for anesthetic use, especially in cardio vascular surgery. It is generally considered to have a shorter duration of action than fentanyl. It has been used with propofol to facilitate intubation, and for total intravenous anesthesia. For a discussion of the drugs used to facilitate intubation and of opioids such as alfentanil used to control the pressor response and the rise of intraocular pressure associated
with intubation. For reference to a study indicating that pretreatment with alfentanil can reduce the pain associated with injection of propofol, see:
CAESAREAN SECTION
UK licensed product information contraindicates the use of alfentanil before clamping the cord during caesarean section because of the risk of respiratory depression in the neonate. A study of alfentanil 30 micrograms/kg in women undergoing caesarean section was abandoned after massive respiratory depression had occurred in 4 of 5 neonates. Another study 2 in patients undergoing elective caesarean section found that although maternal haemodynamic responses to intubation were minimized when alfentanil 10 micrograms/kg was given intravenously immediately before induction, neonates in the alfentanil group had lower Apgar scores compared with those in the placebo group. However, alfentanil has been used successfully to minimize hemodynamic responses to intubation and surgery in patients with severe cardiovascular disorders undergoing caesarean section.
A baby delivered after the successful use of alfentanil 35 micrograms/kg in a mother with severe aortic stenosis was apnoeic and unresponsive with poor muscle tone; the baby responded rapidly to naloxone. Alfentanil 10 micrograms/kg immediately before induction attenuated the cardiovascular response to intubation in patients with severe pregnancy-induced
hypertension and was considered a suitable alternative to fentanyl 2.5 micrograms/kg; no effect on neonatal mortality could be attributed to anesthetic technique. However, it has been suggested that the use of smaller doses of alfentanil of 7.5 micrograms/kg with magnesium sulfate 30 mg/kg may provide better cardiovascular control.
1. Leuwer M, et al. Pharmacokinetics and pharmacodynamics of an equipotent fentanyl and alfentanil dose in mother and infant during caesarean section. Br J Anaesth 1990; 64: 398P-399P.
2. Gin T, et al. Alfentanil given immediately before the induction of
anesthesia for elective cesarean delivery. Anesth Analg 2000; 90: 1 1 67-72.
3. Redfern N, et al. Alfentanil for caesarean section complicated by severe aortic stenosis: a case report. Br J Anaesth 1987; 59: 1 3 09-12 .
4. Rout CC, Rocke DA. Effects of alfentanil and fentanyl on induction of anesthesia in patients with severe pregnancy-induced hypertension. Br J Anaesth 1990; 65: 468-74.
5. Ashton WB, et al. Attenuation of the pressor response to tracheal intubation by magnesium sulphate with and without alfentanil in hypertensive proteinuric patients undergoing caesarean section. Br J Anaesth 1991; 67: 741-7.
PHAEOCHROMOCYTOMA
Alfentanil does not release hist amine and was of value in the anesthetic management of patients with phaeochromocytoma - It has a very rapid onset of action, good vasodilating properties, and a relatively short elimination half-life. These patients are often very somnolent for the first 48 hours after surgery and postoperative opioid dosage requirements may be less than expected. Alfentanil infusion continued into the postoperative period allows careful titration of dosage.
I. Hull CJ. Phaeochromocytoma: diagnosis, preoperative preparation and anesthetic management. Br J Anaesth 1 986; 58:145 3-68.

Pain
POSTOPERATIVE ANALGESIA
Continuous on-demand epidural infusions of alfentanil 200 micrograms/hour or fentanyl 20 micrograms/hour provided comparable analgesia to morphine 200 micrograms/hour in the early postoperative period; alfentanil (16 minutes) and fentanyl (13 minutes) had the advantage of more rapid onset of analgesia than morphine (44 minutes). However, some considered that there was no overall advantage of epidural over intravenous alfentanil either as patient-controlled analgesia or by continuous infusion.
1. Chrubasik J, et al. Relative analgesic potency of epidural fentanyl, alfentanil, and morphine in treatment of postoperative pain. Anesthesiology 1988; 68: 929-33.
2. Chauvin M, et al. Equivalence of postoperative analgesia with patient controlled intravenous or epidural alfentanil. Anesth Analg 1993; 76: 1 2 5 1-8.
3. van den Nieuwenhuyzen MCO, et al. Epidural vs intravenous infusion of alfentanil in the management of postoperative pain following laparotomies. Acta Anesthesia! Scand 1996; 40: 1112-18.

Adverse Effects and Treatment
Effects on the cardiovascular system
Sinus arrest had occurred during intubation in 2 patients given alfentanil 30 micrograms/kg.
1. Maryniak JK, Bishop VA. Sinus arrest after alfentanil. Br J Anaesth 1987; 59: 390-1.
Effects on mental function
Like fentanyl, alfentanil 7.5 or 15 micrograms/kg intravenously had no effect on memory in healthy subjects. In another study impairment of memory for new facts did occur 2 hours after operation in patients anaesthetized with alfentanil 7.5 micrograms/kg, but not in those given fentanyl; methohexital might have contributed to the impairment.
l. Scamman FL, et al. Ventilatory and mental effects of alfentanil and fentanyl. Acta Anesthesia! Scand 1984; 28: 63-7.
2. Kennedy DJ, Ogg TW. Alfentanil and memory function: a comparison with fentanyl for day case termination of pregnancy. Anesthesia 1985; 40: 537-40.
Effects on the respiratory system
Alfentanil, like other opioid agonists, causes dose-related respiratory depression; it is significant with doses of more than 1 mg. Recovery has been reported to be faster after alfentanil than after fentanyl; possibly reflecting the shorter elimination half-life of alfentanil. Even so, accumulation of alfentanil is possible with large doses over a prolonged period. Profound analgesia is accompanied by marked respiratory depression which may persist or recur postoperatively.
Sudden respiratory arrest usually within an hour after the end of alfentanil infusion has been reported in patients who initially appeared to have made a rapid recovery from anesthesia; all responded to treatment with naloxone. Close monitoring of respiration in the initial postoperative period was recommended and this was reinforced by the manufacturers; factors such as hyperventilation and the use of opioid premedication might enhance or prolong the respiratory depressant effects of alfentanil.
1. Andrews CJH, et al. Ventilatory effects during and after continuous infusion of fentanyl or alfentanil. Br J Anaesth 1983;55: 211S-16S.
2. Scamman FL, et al. Ventilatory and mental effects of alfentanil and fentanyl. Acta Anesthesia! Scand 1984; 28: 63-7.
3. Sebel PS, et al. Respiratory depression after alfentanil infusion. BMJ 1984; 289: 1 5 8 1-2.
4. Krane BD, et al. Alfentanil and delayed respiratory depression: case studies and review. Anesth Analg 1990; 70: 5 57-6 1 .
5. Stemlo JEG, Sandin RH. Recurrent respiratory depression after total intravenous anesthesia with propofol and alfentanil. Anesthesia 1998; 53: 378-8 1 .
6. Waldron HA, Cookson RF. Respiratory depression after alfentanil infusion. BMJ 1985; 290: 319.

Precautions
Children
Alfentanil given to preterm infants undergoing paralysis and mechanical ventilation for respiratory distress syndrome resulted in a rapid and significant fall in heart rate and blood pressure, emphasizing that proper evaluation of the pharmacological and clinical effects was necessary. The half-life of alfentanil is prolonged in neonates and accumulation is likely with prolonged use; muscle rigidity may occur and the use of muscle relaxants may be required.
1. Marlow N, et al. Hazards of analgesia for newborn infants. Arch Dis Child 1988; 63: 1293.
The elderly
EEG changes suggested that elderly patients had increased brain sensitivity to alfentanil, and that lower doses might be indicated in older patients for pharmacodynamic rather than pharmacokinetic reasons.
I. Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose requirements with age: a simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 1987; 240: 159-66.
Handling
Avoid contact with the skin and the inhalation of particles of al!entanil hydrochloride.
Inflammatory bowel disease
Patients with Crohn's disease required higher doses of alfentanil than control patients although there were no differences in alfentanil pharmacokinetics between the 2 groups of patients.
1. Gesink-van der Veer BJ, et al. Influence of Crohn's disease on the pharmacokinetics and pharmacodynamics of alfentanil. Br J Anaesth 1993; 71: 827-34.
Porphyria
The Drug Database for Acute Porphyria, compiled by the Norwegian Porphyria Center (NAPOS) and the Porphyria Center Sweden, classifies alfentanil as probably not porphyrinogenic; it may be used as a drug of first choice and no precautions are needed. 1. The Drug Database for Acute Porphyria. Available at: http:l/www. drugs-porphyria.org (accessed 22/ 1 0/ 1 1 )
Pregnancy
UK licensed product
information contra-indicates the use of alfentanil in labor, or before clamping of the cord during caesarean section, because placental transfer means there is a risk of neonatal respiratory depression.

Interactions
Drugs that depress the heart or increase vagal tone, such as beta blockers and anesthetic drugs, may predispose patients given alfentanil to develop bradycardia and hypotension. Use of alfentanil with non-vagolytic neuromuscular blockers may produce bradycardia and possibly asystole. The metabolism of alfentanil via the cytochrome P450 isoenzyme CYP3A4 may be reduced by potent inhibitors of this isoenzyme, resulting in a risk of prolonged or delayed respiratory depression. Reduced doses of alfentanil may be required if given with a CYP3A4 inhibitor such as cimetidine, diltiazem, erythromycin, fluconazole, itraconazole, ketoconazole, or ritonavir.
Antibacterials
The elimination half-life of alfentanil was increased and clearance decreased when given after a 7 day course of oral erythromydn in healthy subjects. Prolonged respiratory depression has also occurred in a 32-year-old man given alfentanil during anesthesia after three 1-g doses of erythromycin in the 24 hours before surgery. In another study of healthy subjects, the clearance (three-compartment model) of alfentanil was reduced by 70% in those given oral tro/eandomydn Other hepatic enzyme inhibitors and drugs interfering with hepatic blood flow might also affect the clearance of alfentanil.
l. Bartkowski RR, et al. Inhibition of alfentanil metabolism by erythromycin. Clin Pharmarol Ther 1989; 46: 99-102.
2. Bartkowski RR. McDonnell TE. Prolonged alfentanil effect following erythromycin administration. Anesthesiology 1990; 73: 566-8.
3. Kharasch ED, et al. The role of cytochrome P450 3A4 in alfentanil clearance: implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology 1997; 87: 36-50.
Antifungals
Azole antifungals such as fluconazole, ketoconazole, or voriconazole can inhibit the metabolism of alfentanil. In a study, giving alfentanil 1 hour after intravenous or oral fluconazole decreased the clearance of alfentanil by 60 and 55%, respectively, and increased the mean half-life of alfentanil from 1.5 hours to 2.7 and 2.5 hours, respectively. Similarly, another study found that giving alfentanil 1 hour after oral voriconazole decreased the clearance of alfentanil by 85% and increased the mean half-life of alfentanil to 6.6 hours.
1. Palkama VJ, et al. The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. Anesth Analg 1998; 87: 190-4.
2. Saari TI, et al. Voriconazole, but not terbinafine, markedly reduces alfentanil clearance and prolongs its half-life. Clin Pharmacol Ther 2006; 80: 502-8.

Pharmacokinetics
After parenteral doses alfentanil hydrochloride has a rapid onset and short duration of action. Alfentanil is about 90% protein bound and has a small volume of distribution. Its terminal elimination half-life is about 1 to 2 hours. It is metabolized in the liver; oxidative N- and O-dealkylation by the cytochrome P450 isoenzyme CYP3A4 leads to inactive metabolites, which are excreted in the urine. Alfentanil crosses the blood-brain barrier and the placenta and has been detected in colostrum. Alfentanil is less lipid-soluble than fentanyl. but more so than morphine. It is highly bound to plasma proteins, mainly to a1-acid glycoprotein. Decreased lipid solubility can be expected to limit penetration of the blood-brain barrier when compared with fentanyl, but the majority of unbound alfentanil is unionized and can rapidly gain access to the CNS. Alfentanil has a smaller volume of distribution than fentanyl and its elimination half-life is shorter. The manufacturers have given values for a three-compartment pharmacokinetic model with a distribution half-life of 0.4 to 3.1 minutes, a redistribution half-life of 4.6 to 21.6 minutes, and a terminal elimination half-life of 64 to 129.3 minutes after a single bolus injections of 50 or 1 2 5 micrograms/kg. Accumulation is less likely than with fentanyl but can occur after repeated or continuous dosage especially in patients with reduced clearance. The mean elimination half-life reported is usually about 90 minutes, but this is reduced in children and increased in the elderly
and neonates, in hepatic impairment, in the obese, and during cardiopulmonary bypass.
Reviews:
I. Hull CJ. The pharmacokinetics of alfentanil in man. Br J Anaesth 1983; 55 (suppl 2): 1575-1645.
2. Mather LE. Clinical pharmacokinetics of fentanyl and its newer derivatives. Clin Phannacokinet 1 983; 8: 422-46.
3. Davis PJ, Cook DR. Clinical pharmacokinetics of the newer intravenous anesthetic agents. Clin Pharmacokinet 1986; 11: 18-35.
4. Bodenham A, Park GR. Alfentanil infusions in patients requiring intensive care. Clin Pharmacokinet 1988; 15:216-26.
5. Scholz J, et al. Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil. Clin Pharmacokinet 1996; 31: 275-921

Administration
CONTINUOUS INTRAVENOUS INFUSION
Small studies of alfentanil by continuous intravenous infusion1-3 have found pharmacokinetic parameters to be similar to those after a single bolus injection, but with some conflicting results. In 29 patients undergoing orthopedic surgery an initial bolus intravenous injection of alfentanil 50 micrograms/kg was followed by intravenous infusion of I microgram/kg per minute, continued for 44 to 445 minutes; a second bolus injection of 50 micrograms/kg was given immediately before injection and an additional bolus injection of 1 mg given if necessary.
The time course of the plasma-alfentanil concentration fitted a two-compartmental model in 26 patients. Terminal half-lives varied widely from 56 to 226 minutes (mean 106 minutes), the
highest values being mainly in patients over 60 years. There was no significant correlation between pharmacokinetic parameters and the duration of the infusion or the total dose. Plasma clearance and volumes of distribution did not correlate significantly with body-weight although steady-state volume of distribution was enlarged with increasing age. The mean estimated steady-state concentration was 293 nanograms/mL (range 147 to 636 nanograms/mL).
I. Fragen RJ, eta!. Pharmacokinetics of the infusion of alfentanil in man. Br J Anaesth 1983; 55: 1077-81.
2. Shaffer A, et al. Pharmacokinetics and pharmacodynamics of alfentanil infusions during general anesthesia. Anesth Analg 1986; 65: 1 021-8.
3. Reitz JA, et al. The pharmacokinetics of alfentanil in gynecologic surgical patients. J Clin Pharmacol 1986; 26: 60--4.
4. van Beem H, et al. Pharmacokinetics of alfentanil during and after a fixed rate infusion. Br J Anaesth 1989; 62: 610-15.
INTRAMUSCUlAR
See The Elderly, below
Burns
The volume of distribution and total clearance of alfentanil were reduced and its elimination half-life prolonged in patients with bums. This was due, in part, to raised concentrations of a 1-acid glycoprotein leading to increased protein binding.
1. Macfie AG, et al. Disposition of alfentanil in bums patients. Br J Anaesth 1992; 69: 447-50.
Cardiopulmonary bypass
The elimination half-life of alfentanil increased from 72 minutes before cardiopulmonary bypass to 195 minutes afterwards in 5 patients.
This was attributed to an increase in volume of distribution, based in part on a dilution-induced decrease in plasma protein binding. Others2,3 found that on starting cardio pulmonary bypass total serum concentrations of alfentanil were halved, mainly because of dilution of u1-acid glyco protein and an increase in unbound alfentanil.
I. Hug CC, et al. Alfentanil pharmacokinetics in patients before and after cardiopulmonary bypass. Anesth Analg 1983; 62: 266.
2. Kumar K, et al. The effect of cardiopulmonary bypass on plasma protein binding of α!fentanyl. Bur J Clin Pharmacol 1988; 35: 47-52.
3. Hynynen M, et al. Plasma concentration and protein binding of
alfentanil during high-dose infusion for cardiac surgery. Br J Anaesth 1994; 72: 571-6.

Children
Alfentanil has been shown to have a shorter elimination half-life (about 40 minutes) and a smaller volume of distribution in children than in adults.
However, the half-life of alfentanil is prolonged in neonates.
See also Hepatic Impairment, below.
I. Meistelman C, et a!. A comparison of alfentanil pharmacokinetics in children and adults. Anesthesiology 1987; 66:13-16.

The elderly
Plasma clearance of alfentanil after a single intravenous dose of 50 micrograms/kg was reduced in patients more than 65 years old when compared with that in healthy young adults. Mean elimination half-life was 137 minutes in the elderly and 83 minutes in the young adults. Volumes of distribution were similar and it was considered that reduced clearance might be due to decreased hepatic metabolism in the elderly. In a study in male patients the terminal elimination half-life of alfentanil increased with age, although clearance was not significantly affected. In patients given alfentanil I microgram/kg per minute by continuous intravenous infusion during orthopedic surgery, terminal half-life increased linearly with age in those older than 40 years and steady state volume of distribution was enlarged with increasing age; clearance did not correlate significantly with age and was thought to be more variable during a continuous infusion in long-term surgery than after a single bolus injection. Others have reported4 that the effects of age on alfentanil pharmacokinetics are dependent on gender. In this study total plasma clearance decreased and terminal half-life increased with increasing age in women, but not in men. It has been suggested that this effect in women may be more dependent on menopausal status than on
age. In a study6 in elderly patients plasma concentrations of alfentanil were greater and the maximum concentration occurred earlier when alfentanil was injected into the deltoid muscle compared with injection into the gluteal muscle.
I. Helmers H, et al. Alfentanil kinetics in the elderly. Clin Pharmacol Ther 1984; 36: 239-43.
2. Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose
requirements with age: a simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacal Bxp Ther 1987; 240: 159-66.
3. van Beem H, et al. Pharmacokinetics of alfentanil during and after a fixed rate infusion. Br l Anaesth 1989; 62: 610-15.
4. Lemmens HJM, et al. Influence of age on the pharmacokinetics of alfentanil: gender dependence. Clin Pharmacokinet 1990; 19: 416-22.
5. Rubio A, Cox C. Sex, age and alfentanil pharmacokinetics. Clin
Pharmacokinet 1991; 21: 81.
6. Virkkilii M, et al. Pharmacokinetics and effects of i.m. alfentanil as premedication for day-case ophthalmic surgery in elderly patients. Br J Anaesth 1993; 71: 507-l l .
Hepatic impairment
Total plasma clearance and protein binding of alfentanil were decreased in patients with alcoholic cirrhosis when compared with control subjects. Elimination half-life was prolonged from 90 to 2 1 9 minutes in the cirrhotic patients following a single intravenous dose of 50 micrograms/kg and was attributed in part to alterations in binding sites of a1-acid glycoprotein. There might be different effects on alfentanil disposition in patients with non-alcoholic cirrhosis or other liver disorders. The pharmacokinetics of alfentanil were apparently not affected in children with cholestatic hepatic disease, whereas clearance was reduced postoperatively in 3 patients who had undergone liver transplantation.
I. Ferrier C, et al. Alfentanil pharmacokinetics in patients with cirrhosis. Anesthesiology 1985; 62: 480--4.
2. Bower S, et al. Effects of different hepatic pathologies on disposition of alfentanil in anaesthetized patients. Br J Anaesth 1992; 68: 462-5.
3. Davis PJ, et al. Effects of cholestatic hepatic disease and chronic renal failure on alfentanil pharmacokinetics in children. Anesth Analg 1989; 68: 579-83.

Obesity
The pharmacokinetics of alfentanil are reportedly altered in obesity. Elimination half-life was 172 minutes in 6 obese patients compared with 92 minutes in 7 who were not obese. Plasma clearance of alfentanil was also decreased, although others 2 found that obesity had no effect on clearance, but it did have a direct relationship with the volume of the central compartment.
1. Bentley JB, et al. Obesity and alfentanil pharmacokinetics. Anesth Analg 1983; 62: 2 5 1 .
2. Maitre PO, et al. Population pharmacokinetics of alfentanil: the average dose-plasma concentration relationship and interindividual variability in patients. Anesthesiology 1987; 66: 3-12.
Renal impairment
The pharmacokinetics of alfentanil were not affected significantly in adults or children 2 with chronic renal failure. In another study increased volume of distribution of alfentanil at steady state was associated with decreased plasma protein _ binding in patients with chronic renal failure.
I. Van Peer A, et al. Alfentanil kinetics in renal insufficiency. Bur J Clin Pharmacol i986; 30: 245-7.
2. Davis PJ, et al. Effects of cholestatic hepatic disease and chronic renal failure on alfentanil pharmacokinetics in children. Anesth Analg 1989; 68: 579-83.
3. Chauvin M, et al. Pharmacokinetics of alfentanil in chronic renal failure. Anesth Analg 1987; 66: 53-6.

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