Pharmacokinetics fentanyl

The average drug input fluxes during the 20 min dosing periods between hours 24 and 25 were calculated to be 81, 108, and 138pg/h/cm for currents of 150, 200, and 250 pA, respectively. These values, the mean maximum plasma concentration values, and the total AUC values (over the same time period) for the three IDDS treatments all increased proportionally with current. These results agree with theoretical expectations expressed by [Eq. (1)]. In addition, the variabilities in the fentanyl pharmacokinetic parameters were similar for the IDDS and IV treatments, indicating that the IDDS doses were delivered with an accuracy similar to the IV infusions. 

Holley, F.O. van Steennis, C. Postoperative analgesia with fentanyl pharmacokinetics and pharmacodynamics of constant-rate IV and transdermal delivery. Br. J. Anaesthesia. 1988, 60, 608-613. 

Irazuzta, J.E., Ahmad, U., Gancayaco, A., Ahmed, S.T., Zhang, J. and Anand, K.J.S. (1996) Intratracheal administration of fentanyl pharmacokinetics and local tissue effects. Intensive Care Medicine, 22, 129-133. 

Mather LE, Woodhouse A, Ward ME, Earr SJ. Pulmonary administration of aerosolised fentanyl Pharmacokinetic analysis. BrJ Anaesth 1998 46 37-43. 

Darwish M, Kirby M, Robertson P, Tracewell W, and Jiang JG (2006) Pharmacokinetic properties of fentanyl effervescent buccal tablets A phase I, open-label, crossover study of single dose 100, 200, 400, and 800 micrograms in healthy adult volunteers. Clin. Ther. 28 707-714. 

G. Duarte, and S.P. da Cunha. Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women. Eur I Clin Pharmacol. 61 517-522 (2005). 

Pharmacokinetic properties Intravenous alfentanil (Hull, 1983) has a rapid onset and a short duration of action. It has a shorter elimination time (terminal half-life 1-2 h) than fentanyl. It is less lipid-soluble and the short duration of action is more dependent on metabolic inactivation than on redistribution. Alfentanil has a high (90%) plasma protein binding. Metabolic inactivation is effected by oxidative N- and O-demethylation. 

Pharmacokinetic properties Fentanyl (Scholz et al., 1996) is a highly lipophilic compound and about 80% binds to plasma proteins. After parenteral administration it has a rapid onset and a short duration of action. The compound is rapidly transported into the CNS and lipid tissues. The short duration of action is due to redistribution rather than metabolic inactivation or excretion. It is released from tissue depots with a half-life of about 4 h and the terminal half-life is up to 7 h. The main metabolites, excreted in urine are 4-N-(N-propionylanilino)-piperidine and the N-hydroxypropionyl derivative. 

Scholz, J., Steinfath, M., Schulz, M. Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil. An update, Clin. Pharmacokinet. 1996, 31, 275-292. 

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

Thysman S., and V. Preat. 1993. In vivo iontophoresis of fentanyl and sufentanil in rats Pharmacokinetics and acute antinociceptive effects. Anesth Analges 11 (1) 61. 

Sinatra, R. (2005), The fentanyl FI Cl patient-controlled transdermal system (PCTS) An alternative to intravenous patient-controlled analgesia in the postoperative setting, Clin. Pharmacokinet., 44(Suppl 1), 1-6. 

Scott JC, Stanski DR. Decreased fentanyl and alfen-tanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 1987 240 159-66. 

Gupta, S.K. Southam, M. Sathyan, G. Klausner, M. Effect of current density on pharmacokinetics following continuous or intermittent input from a fentanyl electrotransport system. J. Pharm. Sci. 1998, 87, 976-981. 

Shaefer, S.L. Varvel, J.R. Aziz, N. Scott, J.C. Pharmacokinetics of fentanyl administered by computer-controlled infusion pump. Ajuesthesiology 1990, 75, 1091-1102. 

Even small doses of fentanyl can cause respiratory depression. Delayed respiratory depression can be a particular problem in the elderly, in whom the half-life is approximately three times longer than in younger patients (6). Respiratory depression has been reversed with nalbuphine doxapram could only antagonize this effect for 2-5 minutes (7). However, the need for prolonged treatment of respiratory depression with naloxone, because of pharmacokinetic variability and/or transdermal drug reservoir, has been emphasized by several authors (SEDA-16, 80) (SEDA-17, 80). 

Grond S, Radbruch L, Lehmann KA. Clinical pharmacokinetics of transdermal opioids focus on transdermal fentanyl. Clin Pharmacokinet 2000 38(l) 59-89. 

Fentanyl is a substrate of CYP3A4, CYP2C9, and CYP2C19. However, in one study, the pharmacokinetics... 

The adverse effects reported with epidural administration are similar to those reported with the intrathecal route. Again, old age and respiratory disease probably dispose to respiratory depression (133). As can be predicted from pharmacokinetic considerations, delayed respiratory depression is more common with epidural morphine than with fentanyl (134). 

Wierda JM, Kleef UW, Lambalk LM, Kloppenburg WD, Agoston S. The pharmacodynamics and pharmacokinetics of Org 9426, a new non-depolarizing neuromuscular blocking agent, in patients anaesthetized with nitrous oxide, halothane and fentanyl. Can J Anaesth 1991 38(4 Pt l) 430-5. 

Fentanyl is a jl receptor agonist that significantly increases locomotor activity in horses (0.02 mg/kg). Addition of a specific k receptor agonist (U50,488H) to fentanyl enhanced the loco-motory effect, with a more rapid onset and longer duration. This may indicate that locomotor activity is mediated by both jjl and k receptors or it may be the result of altered pharmacokinetics of fentanyl in the presence of the second drug (Mama et al 1993). Fentanyl (0.01-0.05 mg/kg i.v.) caused marked inhibition of propulsive activity in the equine colon with closure of the cecocolic sphincter that lasted for 60-120 min (Roger et al 1994). 

Fentanyl (0.001 mg/kg i.v.) can be used with xylazine (0.44 mg/kg i.v.) for anesthetic premedication. Fentanyl is sometimes used as an anesthetic adjunct during inhalation anesthesia to improve analgesia. The pharmacokinetics of fentanyl make it ideal for administration by constant rate infusion and it can be administered intra-operatively at a rate of 0.001-0.004 mg/kg/h after a 0.001 mg/kg loading dose. To prevent excitement or locomotory stimulation in recovery, the infusion should be discontinued 30 min prior to recovery or the horse should be sedated with xylazine (0.1 mg/kg i.v.) prior to recovery. 

Artru A A 1990 Hypocapnia and diazepam reverse and midazolam or fentanyl attenuates ketamine induced Increase of cerebral blood volume and/or cerebrospinal fluid pressure. In Domino E F (ed) Status of ketamine in anesthesiology. NPP Books, Ann Arbor, Ml, p. 119 Aurich C, Aurich J E, Klug E 1993 Naloxone affects gastrointestinal functions and behaviour in horses. Deutsche Tierarztiiche Wochenschrift 100 314-315 Ballard S, Shults T, Kownacki A A et al 1982 The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse. 

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