Abstract
We studied the pharmacokinetic disposition of alfentanil in 20 volunteers and in 15 surgical patients 20-72 years old. Pharmacokinetic disposition was first order and was well described by a two-compartment open model. Centralcompartment volume of distribution was 0.131 ± 0.087 L · kg-1 (mean ± SD) in young healthy volunteers and decreased modestly with increasing age (r = - 0.32, P < 0.05). However, apparent volume of distribution at steady-state, 0.404 ± 0.205 L · kg-1 for the whole study cohort, was not age-related. Plasma clearance of alfentanil in young healthy subjects, 9.3 ± 6.3 ml · kg-1min-1, also showed an inverse relationship with age (r = -0.54, P < 0.001), and was not affected by surgical stress in subjects older than 60 years. Cigarette smoking and sex of the subjects did not contribute to interindividual differences in the kinetic disposition of this drug. Our finding that interindividual differences in disposition of alfentanil were the least in older subjects suggests that its pharmacological effects related to pharmacokinetic disposition should be most predictable in the elderly.
Résumé
On a étudié la disposition pharmacocinétique de ľalfentanil chez 20 volontaires en bonne santé et chez 15 patients chirurgicaux âgés de 20 à 72 ans. La disposition pharmacocinétique était du premier ordre et était bien décrite par le modèle ouvert à deux compartiments. Le volume du compartiment central de distribution était de 0.131 ± 0.028 L ·kg-1 (moyenne ± SM) chez des patients volontaires en bonne santé et diminuant légèrement avec ľaugmentation de ľâge (r = -0.32, P < 0.05). Cependant, le volume apparent de distribution après équilibration était de 0.404 ± 0.035 L ·kg-1 pour tous les patients de ľétude et n’était pas en relation avec ľâge. La clearance plasmatique de ľalfentanil chez des sujets jeunes en bonne santé était de 9.3 ± 2.0 ml·kg-1 -min-1, a aussi démontré une relation inverse avec ľâge (r = 0.54, P < 0.001), et n’était pas affectée par le stress chirurgical chez les sujets plus âgés que 60 ans. Le tabagisme et le sexe des sujets n’a pas contribué à des différences dans la disposition de cette drogue. On a trouvé que les différences entre les individus dans la disposition de ľalfentanil étaient moindres chez les sujets âgés suggérant que ses effets pharmacologiques reliés à la disposition pharmacocinétique doivent être plus prévisibles chez les gens âgés.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Sebel PS, Bovili JG, van der Haven A. Cardiovascular effects of alfentanil anaesthesia. Br J Anaesth 1982; 54: 1185–90.
Davis PJ, Cook DR. Clinical pharmacokinetics of the newer intravenous anesthetic agents. Clin Pharmacokinet 1986; 11: 18–35.
Bovili JG, Sebel PS, Blackburn CL, Heykants J. The pharmacokinetics of alfentanil (R39209): a new opioid analgesic. Anesthesiology 1982; 57: 439–43.
Bower S, Hull CJ. Comparative pharmacokinetics of fentanyl and alfentanil. Br J Anaesth 1982; 54: 871–7.
Chauvin M, Lebrault C, Levron JC, Duvaldestin P. Pharmacokinetics of alfentanil in chronic renal failure. Anesth Analg 1987; 66: 53–6.
Gepts E, Heytens L, Camu F. Pharmacokinetics and placental transfer of intravenous and epidural alfentanil in parturient women. Anesth Analg 1986; 65: 1155–60.
Helmers H, van Peer A, Woestenborghs R, Noorduin H, Heykants J. Alfentanil kinetics in the elderly. Clin Pharmacol Ther 1984; 36: 239–43.
Meistelman C, Saint-Maurice C, Lepaul M, Levron J-C, Loose J-P, Mac Gee K. A comparison of alfentanil pharmacokinetics in children and adults. Anesthesiology 1987; 66: 13–6.
Shafer A, Sung M-L, While PF. Pharmacokinetics andpharmacodynamics of alfentanil infusions during general anesthesia. Anesth Analg 1986; 65: 1021–8.
van Peer A, Vercauteren M, Noorduin H, Woestenborghs R, Heykants J. Alfentanil kinetics in renal insufficiency. Eur J Clin Pharmacol 1986; 30: 245–7.
Camu F, Gepts E, Rucquoi M, Heykants J. Pharmacokinetics of alfentanil in man. Anesth Analg 1982; 61: 657–61.
Reitz JA, Howie MB, Hoffer L, Kryc J, MacKichan JJ. The pharmacokinetics of alfentanil in gynecologic surgical patients. J Clin Pharmacol 1986; 26: 60–4.
Yate PM, Thomas D, Short SM, Sebel PS, Morton J. Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients on the ITU. Br J Anaesth 1986; 58: 1091–9.
Maitre PO, Vozeh S, Heykants J, Thomson DA, Stanski DR. Population pharmacokinetics of alfentanil: the average dose-plasma concentration relationship and interindividual variability in patients. Anesthesiology 1987; 66: 3–12.
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.
American Society of Anesthesiologists. New classification of physical status. Anesthesiology 1963; 24: 111.
Phipps JA, Sabourin MA, Buckingham W, Strunin L. Detection of picogram concentrations of fentanyl in plasma by gas-liquid chromatography. J Chromatogr 1983; 272: 392–5.
Gillespie TJ, Gandolfi AJ, Maiorino RM, Vaughan RW. Gas chromatographic determination of fentanyl and its analogues in human plasma. J Anal Toxicol 1981; 5: 133–7.
Statistical Consultants Inc. PCNONLIN and NONLIN84: software for the statistical analysis of nonlinear models. The American Statistician 1986; 40: 52.
Wilkinson L. SYSTAT: the system for statistics. Evanston, Illinois, Systat Inc. 1986.
Kato R. Drug metabolism under pathological and abnormal physiological states in animals and man. Xenobiotica 1977; 7: 25–92.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sitar, D.S., Duke, P.C., Benthuysen, J.L. et al. Aging and alfentanil disposition in healthy volunteers and surgical patients. Can J Anaesth 36, 149–154 (1989). https://doi.org/10.1007/BF03011438
Issue Date:
DOI: https://doi.org/10.1007/BF03011438