Advanced Continuous Simulation

RS Thomas, WE Lytle, TJ Keefe, AA Constan, RSH Yang. Incorporating Monte Carlo simulation into physiologically based pharmacokinetic models using advanced continuous simulation language (ACSL) A computational method. Fundam Appl Toxicol 31 19-28, 1996. 

Eqs. (2.14), (2.30), and (2.31) with Eq. (2.9) can be solved simultaneously without simplification. Since the analytical solution of the preceding simultaneous differential equations are not possible, we need to solve them numerically by using a computer. Among many software packages that solve simultaneous differential equations, Advanced Continuous Simulation Language (ACSL, 1975) is very powerful and easy to use. 

Advanced Continuous Simulation Eanguage User Guide Reference Manual. Concord, MA Mitchell and Gauthier, Assoc., Inc.,1975. 

Eq. (3.34) cannot be solved analytically because it is a nonlinear differential equation. It can be solved by various numerical techniques. Again Advanced Continuous Simulation Language (ACSL, 1975) can be used to solve the problem. Since Eq. (3. 34) is a second-order differential equation, it has to be changed to two simultaneous first-order differential equations to be solved by ACSL as... 

You can solve Eqs. (6.23) and (6.24) to calculate the change of Cx and Cs with respect to time, which involves the solution of a nonlinear equation. Alternatively, the Advanced Continuous Simulation Language (ACSL, 1975) can be used to solve Eqs. (6.22) and (6.23). 

Numerical integration of the preceding equation by using Advanced Continuous Simulation Language (ACSL) or other method yields... 

Advanced Continuous Simulation Language (ASCL), User Guide/ Reference Manual", Mitchell and Gauthier Associates, Inc., Concord, Mass., 1976. 

AUows graphical PBPK model design and provides parameters for a set of toxic chemicals. Requires the free advanced continuous simulation language (ACSL) viewer from www.acslsim.com... 

In the past, the application of physiologically-based pharmacokinetics was limited by the complexity of the mathematics involved because of the large number of parameters in the models. In recent years, the advances in computer software have overcome this limitation. Thus, earlier this year, Clewell and Andersen (89) reported that by using the Advanced Continuous Simulation Language (ACSL), physiologically-based pharmacokinetic modelling may be carried out on personal computers with reasonably short turn-around times (i.e., execution time, 0.6-8 minutes) and in a user-friendly manner. 

Two separate models based on Dow Advanced Continuous Simulation Language (DACSL) were used in these studies. The first model used laboratory data and parameter estimation to determine the Arrhenius constants for two desired and eight undesired reactions in a process. The second model used the Arrhenius constants, heats of reaction, different physical properties, and reactor parameters (volume, heat transfer properties, jacket control parameters, jacket inlet temperature) to simulate the effect of reaction conditions (concentration, set temperature, addition rate) on the temperature of the reaction mixture, pressure and gas flow rates in the reactor, yield, and assay of the product. The program has been successfully used in two scale-ups where the optimum safe operating conditions, effect of various possible failures, and control of possible abnormal conditions were evaluated. 

ACSL - Advanced Continuous Simulation Language. Reference Manual, Mitchell and Gautier Associates, 1987. 

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