Importance of Early Blood Sampling on Vecuronium Pharmacokinetic and Pharmacodynamic Parameters

Overview

Journal Clin Pharmacokinet

Specialty Pharmacology

Date 1993 Jun 1

PMID 8099862

Citations 7

Authors

J Ducharme

F Varin

D R Bevan

F Donati

Affiliations

Soon will be listed here.

Abstract

The effect of early blood sampling on the description of the vecuronium pharmacokinetic-pharmacodynamic relationship was studied following a bolus injection. Sample collection every 10 sec during the first 2 min showed a high concentration peak at 30 to 40 sec, accounting for an important proportion of the total area under the plasma concentration-time curve (AUC). Neglecting it, using only blood samples drawn at 1 and 2 min (limited sampling), led to a significant overestimation of noncompartmentally derived values of mean residence time, clearance, volume of distribution at steady-state and rate of transfer of vecuronium into the effect compartment. Compartmental pharmacokinetics could not be applied to concentration-time curves constructed with early samples, but limited sampling data were fitted to a 2-compartment model. Derived compartmental pharmacokinetic and pharmacokinetic-pharmacodynamic parameters were similar to those obtained noncompartmentally with complete sampling every 10 sec, because back-extrapolation to time zero contributed to the increase in the AUC. However, compartmental analysis does not provide an accurate description of concentration changes following injection.

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References

Shafer S, Varvel J, Gronert G . A comparison of parametric with semiparametric analysis of the concentration versus effect relationship of metocurine in dogs and pigs. J Pharmacokinet Biopharm. 1989; 17(3):291-304. DOI: 10.1007/BF01061898. View

SHANKS C, Avram M, Fragen R, OHara D . Pharmacokinetics and pharmacodynamics of vecuronium administered by bolus and infusion during halothane or balanced anesthesia. Clin Pharmacol Ther. 1987; 42(4):459-64. DOI: 10.1038/clpt.1987.178. View

Holford N, Sheiner L . Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet. 1981; 6(6):429-53. DOI: 10.2165/00003088-198106060-00002. View

Meistelman C, Lienhart A, Leveque C, Bitker M, Pigot B, VIARS P . Pharmacology of vecuronium in patients with end-stage renal failure. Eur J Anaesthesiol. 1986; 3(2):153-8. View

Yamaoka K, Nakagawa T, Uno T . Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm. 1978; 6(2):165-75. DOI: 10.1007/BF01117450. View

van der Veen F, Bencini A . Pharmacokinetics and pharmacodynamics of Org NC 45 in man. Br J Anaesth. 1980; 52 Suppl 1:37S-41S. DOI: 10.1093/bja/52.suppl_1.37s. View

Bencini A, Scaf A, Sohn Y, Meistelman C, Lienhart A, Kersten U . Disposition and urinary excretion of vecuronium bromide in anesthetized patients with normal renal function or renal failure. Anesth Analg. 1986; 65(3):245-51. View

Chiou W . The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part I). Clin Pharmacokinet. 1989; 17(3):175-99. DOI: 10.2165/00003088-198917030-00004. View

Colquhoun D, Sakmann B . Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. J Physiol. 1985; 369:501-57. PMC: 1192660. DOI: 10.1113/jphysiol.1985.sp015912. View

10.

Fahey M, Morris R, Miller R, Nguyen T, Upton R . Pharmacokinetics of Org NC45 (norcuron) in patients with and without renal failure. Br J Anaesth. 1981; 53(10):1049-53. DOI: 10.1093/bja/53.10.1049. View

11.

SAVAGE D, Sleigh T, Carlyle I . The emergence of ORG NC 45, 1- [2 beta,3 alpha,5 alpha,16 beta,17 beta)-3, 17-bis(acetyloxy)-2-(1-piperidinyl)-androstan-16-yl]-1-methylpiperidinium bromide, from the pancuronium series. Br J Anaesth. 1980; 52 Suppl 1:3S-9S. DOI: 10.1093/bja/52.suppl_1.3s. View

12.

Ducharme J, Varin F, Bevan D, Donati F, Theoret Y . High-performance liquid chromatography-electrochemical detection of vecuronium and its metabolites in human plasma. J Chromatogr. 1992; 573(1):79-86. DOI: 10.1016/0378-4347(92)80477-8. View

13.

Unadkat J, Bartha F, Sheiner L . Simultaneous modeling of pharmacokinetics and pharmacodynamics with nonparametric kinetic and dynamic models. Clin Pharmacol Ther. 1986; 40(1):86-93. DOI: 10.1038/clpt.1986.143. View

14.

Sheiner L, Stanski D, Vozeh S, Miller R, Ham J . Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther. 1979; 25(3):358-71. DOI: 10.1002/cpt1979253358. View

15.

Lien C, Matteo R, Ornstein E, Schwartz A, Diaz J . Distribution, elimination, and action of vecuronium in the elderly. Anesth Analg. 1991; 73(1):39-42. DOI: 10.1213/00000539-199107000-00008. View

16.

Boxenbaum H . Pharmacokinetics: philosophy of modeling. Drug Metab Rev. 1992; 24(1):89-120. DOI: 10.3109/03602539208996291. View

17.

Arden J, Lynam D, Castagnoli K, Canfell P, Cannon J, Miller R . Vecuronium in alcoholic liver disease: a pharmacokinetic and pharmacodynamic analysis. Anesthesiology. 1988; 68(5):771-6. DOI: 10.1097/00000542-198805000-00016. View

18.

Donati F, Varin F, Ducharme J, Gill S, Theoret Y, Bevan D . Pharmacokinetics and pharmacodynamics of atracurium obtained with arterial and venous blood samples. Clin Pharmacol Ther. 1991; 49(5):515-22. DOI: 10.1038/clpt.1991.62. View

19.

Sohn Y, Bencini A, Scaf A, Kersten U, Agoston S . Comparative pharmacokinetics and dynamics of vecuronium and pancuronium in anesthetized patients. Anesth Analg. 1986; 65(3):233-9. View

20.

Lynam D, Cronnelly R, Castagnoli K, Canfell P, Caldwell J, Arden J . The pharmacodynamics and pharmacokinetics of vecuronium in patients anesthetized with isoflurane with normal renal function or with renal failure. Anesthesiology. 1988; 69(2):227-31. DOI: 10.1097/00000542-198808000-00012. View