Simulation of Drug Response
Multiple Dose
Two Compartment Model

A patient with liver disease (61.5 kg) is to receive the muscle relaxant pancuronium bromide by IV bolus to produce effective muscle relaxation (> 85%). For this patient use pharmacokinetic parameters value of A', B', α and β of 3.66 Kg/L, 4.92 Kg/L, 0.075 min-1 and 0.00266 min-1, respectively. The pharmacological parameters ke0, CssEC50% and gamma for this patient are 0.16 min-1, 0.249 mg/L and 4.1, respectively. Martindale, The Extra Pharmacopoeia, 30th ed., Pharmaceutical Press, p 1206-7 suggests an initial dose of 40 to 100 µg per kg body weight IV with a supplemental injection of 10 to 20 µg per kg body weight with significant alteration in the presence of renal or liver disease. [Note: If dose is in mg units of A (and B) become Kg/L x mg / Kg = mg/L].

Parameter Your answers
First Bolus Dose mg  
Second Bolus Dose mg at min
Third Bolus Dose mg at min

Enter your regimen in the table and

Figure 23.1.1 Two Compartment Model Illustrating a Response Compartment

Some Equations

Equation 23.1.1 Drug Concentration in Plasma versus Time

Equation 23.1.2 "Steady State" Drug Concentration in Plasma versus Time
Effectively Mimicking Drug "Concentration" in the Receptor Compartment

Equation 23.1.3 Muscle Relaxant Effect (percent paralysis) versus Concentration, Cpss, the Hill Equation

Parameters and equations from Tovey, C., Stephens, I.D., Triggs, E.J. and Bourne, D.W.A. 1983 Apple II Program to Simulate the Response - Time Profile of Non-Depolarising Muscle Relaxant, Comput. Biol. Med., 13(3), 171-4 and Ramzan, M.I., Somogyi, A.A., Walker, J.S., Shanks, C.A. and Triggs, E.J. 1981 Clinical Pharmacokinetics of the non-depolarising muscle relaxant, Clin. Pharmacokinetics, 6, p25-60
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