Pharmacokinetics alfentanil

Figure 7.6 Structure of remifentanil and its major metabolite formed by ester hydrolysis. contrast, alfentanil has an intermediate hepatic extraction (0.3-0.5) and alfentanil clearance will be sensitive to changes in both liver blood flow and reduced enzyme capacity in patients with liver disease. Although the kidneys play a minor role in the elimination of most opioids, renal disease can influence their pharmacokinetic profile, secondary to alterations in plasma proteins and intra- and extravascular volumes. Neither the pharmacokinetics nor the pharmacodynamics of remifentanil is significantly altered in patients with liver or renal disease.

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. 

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

OPIOIDS ANTIFUNGALS 1, Ketoconazole T effect of buprenorphine 2. Fluconazole and itraconazole T the effect of alfentanil 3. Fluconazole and possibly voriconazole T effect of methadone this is a recognized pharmacokinetic effect but of uncertain clinical significance 1. Ketoconazole 1 the CYP3A4-mediated metabolism of buprenorphine 2.1 clearance of alfentanil 3.1 hepatic metabolism 1. The dose of buprenorphine needs to be 1 (by up to 50%) 2. i dose of alfentanil 3. Watch for T effects of methadone... 

Kent AP, Dodson ME, Bower S. The pharmacokinetics and clinical effects of a low dose of alfentanil in elderly patients. Acta Anaesthesiol Belg 1988 39(l) 25-33. 

Palkama VJ, Isohanni MH, Neuvonen PJ, Olkkola KT. The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. Anesth Analg 1998 87(l) 190-4. 

Alfentanil pharmacokinetics, analgesic efficacy and behavioral effects have been evaluated in the horse. Alfentanil (0.02-0.04 mg/kg i.v.) produces a significant increase in locomotor activity in horses (Pascoe et al 1991). Electroencephalography (EEG) after alfentanil administration (0.04mg/kg) during halothane anesthesia in the horse shows a reduction in the frequency power... 

AG Burm, F Flaak-van der Lely, JW van Kleef, CJ Jacobs, JG Bovill, AA Vletter, RP van den Heuvel, W Onkenhout. Pharmacokinetics of alfentanil after epidural administration. Investigation of systemic absorption kinetics with stable isotope method. Anesthesiology 81 308—315, 1994. 

Willens JS, Myslinski NR. Pharmacodynamics, pharmacokinetics, and clinical uses of fentanyl, sufentanil, and alfentanil. Heart Lung 1993 22 239-51. 

T. D. Egan, C. F. Minto, D. J. Hermann, J. Barr, K. T. Muir, and S. L. Shafer, Remifentanil versus alfentanil comparative pharmacokinetics and pharmacodynamics in healthy adult volunteers. Anesthesiology 84(4) 821-833 (1996). 

S. Bjorkman, D. R. Wada, D. R. Stanski, and W. F. Ebling, Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue modeh. J Pharmacokinet Biopharm 22 381 10 (1994). 

Mertens MJ, Vuyk J, Olofsen E, Bovill JG, Burm AGL. Propofol alters the pharmacokinetics of alfentanil in healthy male volunteers. Anesthesiology (2001) 94,949-57. 

Mertens MJ, Olofsen E, Burm AGL, Bovill JG, Vuyk J. Mixed-effects modeling of the influence of alfentanil on propofol pharmacokinetics. Anesthesiology (2004) 100, 795-805. 

Ibrahim AE, Feldman J, Karim A, Kharasch ED. Simultaneous assessment of drug interactions with low- and high-extraction opioids. Application to parecoxib effects on the pharmacokinetics and pharmacodynamics of fentanyl and alfentanil. Anesthesiology (2003) 98,853-61. 

Parecoxib had no effect on the pharmacokinetics of alfentanil or fentanyl, and celecoxib and rofecoxib appeared not to affect the pharmacokinetics of tramadol Coxibs can reduce the perioperative opioid requirement, but adverse effects are not necessarily reduced. 

Ritonavir markedly increases the levels of fentanyl, and markedly increases alfentanil-induced miosis. Other protease inhibitors such as nelfinavir may have a similar effect Care should also be taken if ritonavir is used with other protease inhibitors as a pharmacokinetic enhancer. 

Terbinaflne 250 mg daily for 3 days had no statistically significant effect on alfentanil pharmacokinetics and no adverse effects were reported. ... 

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