Simulation of Drug Response
Multiple Dose
Two Compartment Model
A
patient with liver disease (51.3 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 3.2 kg/L, 4.89 kg/L, 0.0821 min-1 and 0.00276 min-1, respectively. The pharmacological parameters ke0, CssEC50% and gamma for this patient are 0.16 min-1, 0.244 mg/L and 4.3, 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.
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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