Pharmacokinetics Of Alfentanil Research Articles

The pharmacokinetics of alfentanil in children.

The pharmacokinetics of alfentanil were studied in 18 children (3 months to 14 yr of age) undergoing surgery. Alfentanil was administered as a 30-s infusion of either 50 or 120 micrograms.kg-1. Pharmacokinetic values were independent of dose. There was no correlation between Vdss (Volume of distribution at a steady state, measured as l.kg-1) and age or weight, and there was a weak correlation between clearance and age (r = 0.51, P less than 0.05). Vdss and elimination t1/2 were not different in infants less than 1 yr of age when compared to older children. The mean value of Vdss was 0.419 (SE .028) l.kg-1) for the whole group, and elimination t1/2 was 76.3 (SE 6.5) min. The clearance rate [TBC = 7.9 (SE 0.41) ml.kg-1.min-1] was within the range of values previously determined in adult studies. From these data, it would appear that, although there may be differences in the disposition kinetics between children aged 3 months to 14 yr and those measured in adults in some studies by other investigators, age-related differences within this group were not demonstrable.

Pharmacokinetics of Alfentanil in Chronic Renal Failure

The pharmacokinetics of alfentanil were studied during general anesthesia in nine patients with renal failure and in ten patients with normal renal function. All patients received 0.05 mg/kg alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 8 hr, using a specific radioimmunoassay technique. Protein binding was measured by equilibrium dialysis. Elimination half-life and plasma clearance were similar in both groups. The volume of distribution at steady state was greater (P less than 0.02) in patients with renal failure (405 +/- 86 ml/kg) than in patients with normal renal function (281 +/- 97 ml/kg). Patients with renal failure had a higher (P less than 0.01) alfentanil plasma free fraction (0.19 +/- 0.06) than patients with normal renal function (0.11 +/- 0.03). When kinetic parameters were corrected for protein binding, the unbound volume of distribution and the free drug clearance were unchanged in patients with renal failure. These results suggest that the modification of alfentanil free fraction in renal failure does not induce any change in elimination but may influence the distribution of alfentanil.

The pharmacokinetics of alfentanil in gynecologic surgical patients.

The pharmacokinetics and serum protein binding of alfentanil during continuous intravenous infusion were determined in 11 women who were either healthy (American Society of Anesthesiologists [ASA] physical status 1) or had mild systemic disease (ASA physical status 2). Anesthesia was induced with intravenous thiopental 2 mg/kg and alfentanil 50 micrograms/kg and maintained with constant intravenous alfentanil infusions of 1-3 micrograms/kg/min until approximately ten minutes before the end of surgery. Venous blood samples were obtained after the bolus of alfentanil was administered and at various times during and after the alfentanil infusion. Serum alfentanil concentrations were measured by gas-liquid chromatography. There was considerable interpatient variability in alfentanil pharmacokinetics and serum protein binding. The mean +/- SD alfentanil serum clearance, volume of distribution at steady state (Vss), and elimination half-life were 5.2 +/- 2.0 mL/min/kg, 0.47 +/- 0.1 L/kg, and 97 +/- 52 minutes, respectively. The mean fraction of alfentanil unbound in serum (fu) was 0.18 +/- 0.08. There was a time-dependent decrease in alfentanil serum clearance that correlated with increasing duration of surgery. This decrease in clearance resulted in a prolonged alfentanil half-life. These results indicate there is considerable interpatient variability in the pharmacokinetic parameters and serum protein binding of alfentanil in these patients and suggest that the infusion rate of alfentanil during maintenance anesthesia should be adjusted for individual patient response. Infusion rates may need to be tapered during prolonged operations.

Use of alfentanil in short anaesthetic procedures.

The pharmacokinetics of alfentanil, a new and very short-acting opioid, are discussed. Its use in day-case gynaecological procedures is described, and the results of the initial study presented. Alfentanil is a valuable adjunct to anaesthesia for day-case surgery and for short, painful procedures.

Alfentanil Pharmacokinetics in Patients with Cirrhosis

The pharmacokinetics of alfentanil were studied in 11 patients with alcoholic cirrhosis and 10 control patients during general anesthesia. All patients received 50 micrograms . kg-1 alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 10 h, using a specific radioimmunoassay technique. Protein binding was measured by equilibrium dialysis. Patients with cirrhosis had a significantly lower (P less than 0.01) plasma clearance of alfentanil of 1.6 +/- 1.0 ml . min-1 . kg-1 (mean +/- SD) instead of 3.1 +/- 1.6 ml . min-1 . kg-1 in the controls. The total apparent volume of distribution was similar in the two groups. The elimination half-life was prolonged from 90 +/- 18 min in the controls to 219 +/- 128 min in the cirrhotics (P less than 0.01). Patients with cirrhosis had a higher (P less than 0.01) alfentanil plasma-free fraction (18.6 +/- 9.4%) compared with the control patients (11.5 +/- 3.9%). When kinetic parameters were corrected for protein binding, the unbound volume of distribution and the free drug clearance were decreased significantly in patients with cirrhosis. Since the concentration alpha 1-glycoprotein to which alfentanil mainly is bound in plasma did not differ in the two groups, it is suggested that the increase in the free fraction is caused by an alteration of binding sites of this protein in patients with cirrhosis. Owing to its delayed elimination and increased free fraction, alfentanil will exert a prolonged and pronounced effect in patients with cirrhosis.

PHARMACOKINETICS OF THE INFUSION OF ALFENTANIL IN MAN

The pharmacokinetics of alfentanil under the conditions of an empirically derived 1-h continuous infusion of 3 micrograms kg-1 min-1, with a bolus of 80 micrograms kg-1, both i.v., were determined in five patients. The distribution half-life (mean +/- SD) (7.4 +/- 3.1 min), elimination half-life (86.7 +/- 15.8 min), apparent volume of distribution, Varea (0.44 +/- 0.15 litre kg-1) and elimination clearance (3.33 +/- 0.75 ml kg-1 min-1) were similar to those previously reported for a single bolus of alfentanil. These values for apparent volume of distribution and clearance can be used to calculate correct bolus and infusion doses to maintain any desired steady state plasma concentration using standard formulae: for example, to maintain a steady state plasma concentration of 400 ng ml-1, a bolus dose of 176 micrograms kg-1 and an infusion of 1.3 micrograms kg-1 min1 would be required.

The pharmacokinetics of alfentanil (R39209): a new opioid analgesic.

The pharmacokinetics of alfentanil (R39209), a new short-acting opioid analgesic, have been studied in eleven patients. Six patients were given 50 micrograms/kg alfentanil and five patients 125 micrograms/kg as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 6 h (50 micrograms/kg) or 8-10 h (125 micrograms/kg), using a specific radioimmunoassay technique. Plasma concentrations declined triexponentially in both groups. The initial elimination of alfentanil from the plasma was very rapid with 90% of the administered dose leaving the plasma within 30 min. The average half-lives for the three phases were similar for both groups. The combined mean (+/- SEM) half-lives for the 11 patients for the rapid and slow distribution phases were short (t 1/2 pi = 1.2 +/- 0.26 min, t 1/2 alpha = 11.6 +/- 1.63 min). The elimination half-life, t 1/2 beta was 94 +/- 5.87 min which is considerably shorter than that of other opioids. The mean (+/- SEM) total body clearance was 6.4 +/- 1.39 ml . kg-1 . min-1 and the volume of distribution (Vd) was 0.86 +/- 0.194 l/kg. The latter is considerably less than reported values for the chemically related drug, fentanyl, and suggests that alfentanil may have a lower tissue binding affinity than fentanyl. The rapid elimination and short duration of clinical action suggests the feasibility of repeated administration of alfentanil and its use by continuous intravenous infusion.

COMPARATIVE PHARMACOKINETICS OF FENTANYL AND ALFENTANIL

The pharmacokinetics of fentanyl and alfentanil were compared by the simultaneous i.v. administration of both drugs, measurement of plasma concentrations and compartmental analysis. In addition, plasma protein binding, erythrocyte:plasma partition, and heptane:water partition were compared. Alfentanil was found to have a very much smaller apparent volume of distribution, smaller total clearance, and shorter terminal half-time in plasma. Alfentanil was also found to have a greater plasma protein binding, but in contrast to fentanyl, no binding to erythrocytes. It is concluded that alfentanil is less cumulative than fentanyl, has restricted hepatic clearance, and will exhibit non-linear kinetics at very high doses. An appendix describes the model-fitting procedure in detail.

Blood circulation in adipose tissue

articleBlood circulation in adipose tissueS. Rosell, and E. BelfrageS. Rosell, and E. BelfragePublished Online:01 Oct 1979https://doi.org/10.1152/physrev.1979.59.4.1078MoreSectionsPDF (4 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByInhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limbIlkka Heinonen, Maria Wendelin-Saarenhovi, Kimmo Kaskinoro, Juhani Knuuti, Mika Scheinin, and Kari K. Kalliokoski15 July 2013 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 305, No. 2Role of Uncoupling Proteins in Cancer16 April 2010 | Cancers, Vol. 2, No. 2Renin dynamics in adipose tissue: adipose tissue control of local renin concentrationsJason D. Fowler, Stacy B. Krueth, David A. Bernlohr, and Stephen A. Katz1 February 2009 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 296, No. 2β-Adrenergic Receptors and Regulation of Energy Expenditure: A Family AffairAnnual Review of Pharmacology and Toxicology, Vol. 44, No. 1Human Adipose Tissue Cells Keep Tight Control on the Angiotensin II Levels in Their VicinityJournal of Biological Chemistry, Vol. 277, No. 50Prediction of the volume of distribution of a drug: which tissue-plasma partition coefficients are needed?18 February 2010 | Journal of Pharmacy and Pharmacology, Vol. 54, No. 9Analyte flux through chronically implanted subcutaneous polyamide membranes differs in humans and ratsN. Wisniewski, N. Rajamand, U. Adamsson, P. E. Lins, W. M. Reichert, B. Klitzman, and U. Ungerstedt1 June 2002 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 282, No. 6Model predictions and comparisons for three toxicokinetic models for the systemic transport of trichloroethyleneMathematical and Computer Modelling, Vol. 35, No. 9-10Lipolysis in human adipose tissue during exercise: comparison of microdialysis and a-v measurementsKai Henrik Wiborg Lange, Jeanne Lorentsen, Fredrik Isaksson, Lene Simonsen, Jens Bülow, and Michael Kjær1 March 2002 | Journal of Applied Physiology, Vol. 92, No. 3Systemic nicotine stimulates human adipose tissue lipolysis through local cholinergic and catecholaminergic receptors2 August 2001 | International Journal of Obesity, Vol. 25, No. 8Lipid metabolism during endurance exerciseThe American Journal of Clinical Nutrition, Vol. 72, No. 2Intraneural stimulation elicits an increase in subcutaneous interstitial glycerol levels in humans7 September 2004 | The Journal of Physiology, Vol. 521, No. 2Insulin- and glucagon-independent effects of calcitonin gene—related peptide in the conscious dogMetabolism, Vol. 48, No. 5Application of Physiologic Models to Predict the Influence of Changes in Body Composition and Blood Flows on the Pharmacokinetics of Fentanyl and Alfentanil in PatientsAnesthesiology, Vol. 88, No. 3Physiological and metabolic consequences of obesityMetabolism, Vol. 44β-adrenergic stimulation and abdominal subcutaneous fat blood flow in lean, obese, and reduced-obese subjectsMetabolism, Vol. 44, No. 2Adipose tissue metabolismClinics in Dermatology, Vol. 7, No. 4The nervous system and adipose tissueClinics in Dermatology, Vol. 7, No. 4Beta-adrenoceptor sensitivity of brown and white adipocytes after chronic pretreatment of rats with reserpineBiochemical Pharmacology, Vol. 36, No. 1Patterns of hyperphagia in the Zucker obese rat: A role for fat cell size and number?Brain Research Bulletin, Vol. 14, No. 6Circulatory implications of exercise and heat stressPharmacology & Therapeutics, Vol. 31, No. 1-2Effects of the β-adrenergic receptor agonist pirbuterol on cardiac performance during acute ischaemic left ventricular failure in dogsEuropean Journal of Pharmacology, Vol. 87, No. 4Sympatho-adrenal regulation of adipose tissue blood flow in dog and manGeneral Pharmacology: The Vascular System, Vol. 14, No. 1In vivo α2-adrenoceptor-mediated inhibition of isoproterenol of isoproterenol-stimulated free fatty acid output in dog bone marrow adipose tissueEuropean Journal of Pharmacology, Vol. 76, No. 4Obesity and the heartCurrent Problems in Cardiology, Vol. 5, No. 3 More from this issue > Volume 59Issue 4October 1979Pages 1078-1104 Copyright & PermissionsCopyright © 1979 the American Physiological Societyhttps://doi.org/10.1152/physrev.1979.59.4.1078PubMed386395History Published online 1 October 1979 Published in print 1 October 1979 Metrics

Local xenon 133 clearance from the quadriceps muscle during exercise in man.

Local xenon 133 clearance from the quadriceps muscle during exercise in man.