Use of the circuit simulation program SPICE2 for analysis of the metabolism of anticancer drugs
Tóm tắt
Complex networks of biological processes are analogous to electrical circuits. For each step in a biological or electrical network, flow is dependent on the driving force and the conductivity of the step. The relationship between biological flows and their driving forces can therefore be expressed as relationships between analogous currents and voltages. The time dependence of approach to equilibrium or a steady state is determined by the rates of depletion of material in various compartments. Electrical capacitance is therefore analogous to compartment volume. Once these generalized concepts of flow, force and capacitance are recognized, it becomes clear that computer programs designed for analysis of electrical circuits may be used for simulation of biological networks. A set of simple mathematical descriptions of the individual steps and a diagram showing how the steps are arranged with respect to each other are all that is necessary to perform a simulation; there is no need for computer programming skills or differential equations. The use of SPICE2 for simulation of the cellular and plasma pharmacokinetics of cytosine arabinoside (araC) is described as an example. A network model is developed which considers cellular pharmacokinetics (membrane transport, intracellular phosphorylation and dephosphorylation), and plasma pharmacokinetics following infusions of araC.
Tài liệu tham khảo
Abe, I., S. Saito, K. Hori, M. Suzuki and H. Sato. 1983. “Prediction of Sensitivity to 1-β-d-Arabinofuranosylcytosine by the Plateau Level of its 5′-Triphosphate in Human Lymphoblastic Cell Linesin Vitro.”Eur. J. Cancer Clin. Oncol. 19, 941–944.
Capizzi, R. L., J.-L. Yang, E. Cheng, T. Bjornson, D. Shasraguohe, R.-S. Tan and Y.-C. Cheng 1983. “Alteration of the Pharmacokinetics of High Dose AraC by its Metabolite, High AraU in Patients with Acute Leukemia.”J. clin. Oncol. 1, 763–771.
——, J. P. Rathmell, J. C. White, E. Cheng, Y.-C. Cheng and T. Kute. 1985. “Dose-related Pharmacologic Effects of High-dose Ara-C and Its Self-potentiation.”Semin. Oncol. 12, 65–75.
Cha, S., S. Y. R. Kim, S. G. Kornstein, P. W. Kantoff, K. H. Kim and F. N. M. Naguib. 1981. “Tight Binding Inhibitors—IX: Kinetic Parameters of Dihydrofolate Reductase Inhibited by Methotrexate, an Example of Equilibrium Study.”Biochem. Pharmac. 30, 1507–1515.
Cheng, Y.-C., B. Domin and L.-S. Lee. 1977. “Human Deoxycytidine Kinase: Purification and Characterization of the Cytoplasmic and Mitochondrial Isozymes Derived from Blast Cells of Acute Myelocytic Leukemia Patients.”Biochim. biophys. Acta 481, 481–492.
Gale, R. P. 1979. “Advances in the Treatment of Acute Myelogenous Leukemia.”N. Engl. J. Med. 300, 1189–1199.
Goldman, I. D. 1974. “The Mechanism of Action of Methotrexate—I. Interaction With a Low Affinity Intracellular Site Required for Maximum Inhibition of Deoxyribonucleic Acid Synthesis in L-Cell Mouse Fibroblasts.”Molec. Pharmac. 11, 287–297.
Greco, W. R. and M. T. Hakala. 1979 “Evaluation of Methods for Estimating the Dissociation Constant of Tight Binding Inhibitors.”J. biol. Chem. 254, 12104–12109.
Greenblatt, D. J. and J. Koch-Weser. 1975. “Clinical Pharmacokinetics.”N. Engl. J. Med. 293, 702–705.
Jackson, R. C. 1980. “Kinetic Simulation of Anticancer Drug Interactions.”Int. J. Bio-Med. Comput. 11, 197–224.
— and K. R. Harrap. 1973. “Studies with a Mathematical Model of Folate Metabolism.”Archs Biochem. Biophys. 158, 827–841.
— and — 1979. “Computer Models of Anticancer Drug Interaction.”Pharmac. Ther. 4, 245–280.
—, D. Niethammer and F. M. Huennekens. 1975. “Enzymic and Transport Mechanisms of Amethopterin Resistance in L1210 Mouse Leukemia Cells.”Cancer Biochem. Biophys. 1, 151–155.
Kufe, D. W., P. P. Major, E. R. Egan and G. P. Beardsley. 1980. “Correlation of Cytotoxicity with Incorporation of Ara-C into DNA.”J. biol. Chem. 255, 8997–9000.
—, D. Spriggs, E. M. Egan and D. Munroe. 1984. “Relationship among AraCTP Pools, Formation of (Ara-C) DNA, and Cytotoxicity of Human Leukemic Cells.”Blood 64, 58–64.
May, J. and D. C. Mikulecky. 1982. “The Simple Model of Adipocyte Hexose Transport: Kinetic Features, Effect of Insulin, and Network Thermodynamic Computer Simulations.”J. biol. Chem. 257, 11601–11608.
— and — 1983. “Glucose Utilization in Rat Adipocytes: The Interaction of Transport and Metabolism as Affected by Insulin.”J. biol. Chem. 258, 4771–4777.
Mikulecky, D. C. 1979. “A Network Thermodynamic Two-port Element to Represent the Coupled Flow of Salt and Current: Improved Alternative for the Equivalent Circuit.”Biophys. J. 25, 323–340.
— 1983a. “A Network Thermodynamic Approach to the Hill-King and Altman Approach to Kinetics: Computer Simulation.”Prog. clin. biol. Res. 126, 257–282.
— 1983b. “Network Thermodynamics: a Candidate for a Common Language for Theoretical and Experimental Biology.”Am. J. Physiol. 245, R1-R9.
— and J. J. Feher. 1981. “The Relation between Local and Global Transport Parameters in an Epithelial Membrane having an Asymmetric Transport Mechanism.”J. theor. Biol. 88, 575–587.
— and S. R. Thomas 1978. “A Simple Network Thermodynamic Method for Series-Parallel Coupled Flows. III. Application to Coupled Solute and Volume Flow in Epithelial Membranes.”J. theor. Biol. 73, 697–710.
— and — 1979. “Some Network Thermodynamic Models of Coupled, Dynamic Physiological Systems.”J. Franklin Inst. 308, 309–326.
—, E. G. Huf and S. R. Thomas. 1979. “A Network Thermodynamic Approach to Compartmental Analysis: Na+ Transients in Frog Skin.”Biophys. J. 25, 87–106.
Niethammer, D. and R. C. Jackson. 1975. “Changes of Molecular Properties Associated with the Development of Resistance Against Methotrexate in Human Lymphoblastoid Cells.”Eur. J. Cancer 11, 845–854.
Oken, D. E. 1982. “An Analysis of Glomerular Dynamics in Rat, Dog, and Man.”Kidney Int. 22, 136–145.
—, S. R. Thomas and D. C. Mikulecky. 1981. “A Network Thermodynamic Model of Glomerular Dynamics: Application in the Rat.”Kidney Int. 22, 136–145.
Plagemann, P. G. W., R. Marz and R. M. Wohlhueter. 1978. “Transport and Metabolism of Deoxycytidine and 1-β-d-Arabinofuranosylcytosine into Cultured Novikoff Rat Hepatoma Cells, Relationship to Phosphorylation, and Regulation of Triphosphate Synthesis.”Cancer Res. 38, 978–989.
Rathmell, J., J. C. White and R. L. Capizzi. 1984. “Nucleoside Transport (NT) as a Determinant of Cellular Uptake of Ara-C.”Proc. AACR 25, 231.
Thakker, K. M. 1984. “Pharmacokinetic-Pharmacodynamic Modelling and Simulation Using the Electrical Circuit Simulation Program SPICE2.”Biopharmac. Drug Dispos. 5, 315–333.
—, J. H. Wood and D. C. Mikulecky. 1982. “Dynamic Simulation of Pharmacokinetic Systems Using the Electrical Circuit Analysis Program SPICE2.”Comp. Prog. Biomed. 15, 61–72.
Thomas, S. R. and D. C. Mikulecky. 1978. “A Network Thermodynamic Model of Salt and Water Flow Across the Kidney Proximal Tubule.”Am. J. Physiol. 235, F638-F648.
Weinstein, H. J., T. W. Griffin and J. Feeney. 1982. “Pharmacokinetics of Continuous Intravenous and Subcutaneous Infusions of Cytosine Arabinoside.”Blood 59, 1351–1353.
White, J. C. 1979. “Reversal of Methotrexate Binding to Dihydrofolate Reductase by Dihydrofolate: Studies with Pure Enzyme and Computer Modeling Using Network Thermodynamics.”J. biol. Chem. 254, 10889–10895.
— 1983. “Predictions of a Network Thermodynamics Computer Model Relating to the Mechanism of Methotrexate Rescue by 5-Formyltetrahydrofolate and to the Importance of Inhibition of Thymidylate Synthase by Methotrexate-Polyglutamates.”Adv. exp. Med. 163, 305–326.
— and I. D. Goldman. 1976. “The Mechanism of Action of Methotrexate. IV. Free Intracellular Methotrexate is Required for Maximum Suppression of Tetrahydrofolate Synthesis from Dihydrofolate in Ehrlich Ascites Tumor Cells.”Molec. Pharmac. 12, 711–719.
— and —. 1981. “Methotrexate Resistance in an L1210 Cell Line Resulting from Increased Dihydrofolate Reductase, Decreased Thymidylate Synthetase Activity, and Normal Membrane Transport: Computer Simulations Based on Network Thermodynamics.”J. biol. Chem. 256, 5722–5727
— and D. C. Mikulecky. 1982. “Application of Network Thermodynamics to the Computer modeling of the Pharmacology of Anticancer Agents: A Network Model for Methotrexate Action as a Comprehensive Example.”Pharmac. Ther. 15, 251–291.
— and L. H. Hines 1983. “Binding of RadiolabelledN-(Phosphonacetyl)-l-Aspartate to Aspartate Transcarbamylase from Ehrlich Ascites Tumor Cells.”Biochem. Pharmac. 33, 3645–3648.
— and J. P. Rathmell. 1985. “Inhibition of 1-β-d-Arabinofuranosylcytosine Transport and Net Accumulation by Teniposide and Etoposide in Ehrlich Ascites Cells and Human Leukemic Blasts.”Cancer Res. 44, 3070–3075.
—, S. Loftfield and I. D. Goldman. 1975. “The Mechanism of Action of Methotrexate. III. Requirement of Free Intracellular Methotrexate for Maximal Suppression of [14C]Formate Incorporation into Nucleic Acids and Protein.”Molec. Pharmac. 11, 287–297.
Wyatt, J. L., Jr. 1978. “Network Representation of Reaction-diffusion Systems Far from Equilibrium.”Comp. Prog. Biomed. 8, 180–195.
—, D. C. Mikulecky and J. A. DeSimone. 1980. “Network Modeling of Reaction-Diffusion Systems and their Numerical Solution Using SPICE2.”Chem. Engng Sci. 35, 2115–2128.