Abstract

A mathematical pharmacokinetic and pharmacodynamic model was initially developed which can be used in the clinical operating room setting without interfering with routine clinical care. We determined the pharmacokinetics and pharmacodynamics of commonly used neuromuscular blocking drugs (d-tubocurarine and pancruonium) and common antagonists of a non-depolarizing neuromuscular blockade (neostigmine and pyridostigmine). In order to complete these studies a suitable assay to measure drug concentration in body fluids had to be developed. We implemented an immunoassay technique for measuring d-tubocurarine; a high performance liquid chromatography method was developed for measuring neostigmine and pyridostigmine in body fluids. Most recently, a mass spectrometry method was developed for measuring pancuronium concentrations in body fluids. We then determined the influence of renal failure, hepatic disease and hypothermia on the pharmacokinetics and pharmacodynamics of the drugs listed above.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM026403-06
Application #
3273882
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1979-04-01
Project End
1985-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Segredo, V; Caldwell, J E; Wright, P M et al. (1998) Do the pharmacokinetics of vecuronium change during prolonged administration in critically ill patients? Br J Anaesth 80:715-9
Heier, T; Caldwell, J E; Sharma, M L et al. (1994) Mild intraoperative hypothermia does not change the pharmacodynamics (concentration-effect relationship) of vecuronium in humans. Anesth Analg 78:973-7
Heier, T; Caldwell, J E; Eriksson, L I et al. (1994) The effect of hypothermia on adductor pollicis twitch tension during continuous infusion of vecuronium in isoflurane-anesthetized humans. Anesth Analg 78:312-7
Segredo, V; Caldwell, J E; Matthay, M A et al. (1992) Persistent paralysis in critically ill patients after long-term administration of vecuronium. N Engl J Med 327:524-8
Segredo, V; Shin, Y S; Sharma, M L et al. (1991) Pharmacokinetics, neuromuscular effects, and biodisposition of 3-desacetylvecuronium (Org 7268) in cats. Anesthesiology 74:1052-9
Heier, T; Caldwell, J E; Sessler, D I et al. (1991) Mild intraoperative hypothermia increases duration of action and spontaneous recovery of vecuronium blockade during nitrous oxide-isoflurane anesthesia in humans. Anesthesiology 74:815-9
Heier, T; Caldwell, J E; Sessler, D I et al. (1990) The effect of local surface and central cooling on adductor pollicis twitch tension during nitrous oxide/isoflurane and nitrous oxide/fentanyl anesthesia in humans. Anesthesiology 72:807-11
Fahey, M R; Canfell, P C; Taboada, T et al. (1990) Cerebrospinal fluid concentrations of laudanosine after administration of atracurium. Br J Anaesth 64:105-6
Magorian, T T; Lynam, D P; Caldwell, J E et al. (1990) Can early administration of neostigmine, in single or repeated doses, alter the course of neuromuscular recovery from a vecuronium-induced neuromuscular blockade? Anesthesiology 73:410-4
Segredo, V; Matthay, M A; Sharma, M L et al. (1990) Prolonged neuromuscular blockade after long-term administration of vecuronium in two critically ill patients. Anesthesiology 72:566-70

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