//Created by libAntimony v2.4 model grange_holford_guentert_2001_complete__environment(time_) // Variable initializations: time_ = ; end model grange_holford_guentert_2001_complete__gastrointestinal_compartment_L_dopa(F_c_dopa, A_dopa_c, ka_c_dopa, CL_dopa_0, time_) // Assignment Rules: F_c_dopa := F_H * F_G; F_G := 1; F_H := 1 - CL_H / Q; CL_H := f_H * CL_dopa_0; // Rate Rules: A_dopa_c' = - ka_c_dopa * A_dopa_c; // Variable initializations: A_dopa_c = 101; ka_c_dopa = 1.29; Q = 0.828; f_H = 0.13; CL_dopa_0 = ; time_ = ; end model grange_holford_guentert_2001_complete__body_compartment_L_dopa(C_dopa_c, time_, A_dopa_c, F_c_dopa, ka_c_dopa, CL_dopa) // Rate Rules: C_dopa_c' = (1 / V_dopa) * (ka_c_dopa * A_dopa_c * F_c_dopa - CL_dopa * C_dopa_c); // Variable initializations: C_dopa_c = 0; V_dopa = 0.496; time_ = ; A_dopa_c = ; F_c_dopa = ; ka_c_dopa = ; CL_dopa = ; end model grange_holford_guentert_2001_complete__body_compartment_3_OMD(time_, C_dopa_c, CL_COMT) // Rate Rules: C_OMD_c' = (1 / V_OMD_c) * (CL_COMT * C_dopa_c - CL_OMD_c * C_OMD_c); // Variable initializations: C_OMD_c = 0; CL_OMD_c = 0.00895; V_OMD_c = 0.128; time_ = ; C_dopa_c = ; CL_COMT = ; end model grange_holford_guentert_2001_complete__L_dopa_clearance(CL_dopa, CL_dopa_0, CL_COMT, C1_M) // Assignment Rules: CL_dopa := CL_AADC + CL_COMT + CL_REST; CL_COMT := CL_dopa_0 * 0.1; CL_AADC := CL_AADC0 / (1 + C1_M / ki); CL_AADC0 := CL_dopa_0 * 0.69; CL_REST := CL_dopa_0 * 0.21; // Variable initializations: CL_dopa_0 = 0.823; C1_M = ; ki = 0.00246; end model grange_holford_guentert_2001_complete__gastrointestinal_compartment_benserazide(A_bens, ka_B, F_B, time_) // Rate Rules: A_bens' = - ka_B * A_bens; // Variable initializations: A_bens = 19.51; ka_B = 0.94; F_B = 0.022; time_ = ; end model grange_holford_guentert_2001_complete__central_compartment_benserazide(C_bens_central, CLd_B, time_, A_bens, ka_B, F_B, C_bens_peripheral, CL_bens_total) // Rate Rules: C_bens_central' = (1 / V1_B) * ((ka_B * A_bens * F_B - CL_bens_total * C_bens_central) + CLd_B * (C_bens_peripheral - C_bens_central)); // Variable initializations: C_bens_central = 0; V1_B = 0.202; CLd_B = 0.072; time_ = ; A_bens = ; ka_B = ; F_B = ; C_bens_peripheral = ; CL_bens_total = ; end model grange_holford_guentert_2001_complete__peripheral_compartment_benserazide(C_bens_peripheral, time_, CLd_B, C_bens_central) // Rate Rules: C_bens_peripheral' = (1 / V2_B) * CLd_B * (C_bens_central - C_bens_peripheral); // Variable initializations: C_bens_peripheral = 0; V2_B = 0.127; time_ = ; CLd_B = ; C_bens_central = ; end model grange_holford_guentert_2001_complete__benserazide_clearance(CL_bens_total, CL_Ro) // Assignment Rules: CL_bens_total := CL_B / (1 - fm); CL_Ro := CL_bens_total * fm; // Variable initializations: CL_B = 1.67; fm = 0.15; end model grange_holford_guentert_2001_complete__gastrointestinal_compartment_Ro(A_Ro, ka_M, F_Ro, time_) // Rate Rules: A_Ro' = - ka_M * A_Ro; // Variable initializations: A_Ro = 1.3658; ka_M = 2.47; F_Ro = 1; time_ = ; end model grange_holford_guentert_2001_complete__central_compartment_Ro(C_Ro_central, CLd_M, time_, C_bens_central, CL_Ro, A_Ro, ka_M, F_Ro, C_Ro_peripheral) // Rate Rules: C_Ro_central' = (1 / V1_M) * ((ka_M * A_Ro * F_Ro - CL_M * C_Ro_central) + CL_Ro * C_bens_central + CLd_M * (C_Ro_peripheral - C_Ro_central)); // Variable initializations: C_Ro_central = 0; V1_M = 0.0691; CLd_M = 1.06; CL_M = 4.29; time_ = ; C_bens_central = ; CL_Ro = ; A_Ro = ; ka_M = ; F_Ro = ; C_Ro_peripheral = ; end model grange_holford_guentert_2001_complete__peripheral_compartment_Ro(C_Ro_peripheral, time_, CLd_M, C_Ro_central) // Rate Rules: C_Ro_peripheral' = (1 / V2_M) * CLd_M * (C_Ro_central - C_Ro_peripheral); // Variable initializations: C_Ro_peripheral = 0; V2_M = 3.2; time_ = ; CLd_M = ; C_Ro_central = ; end model *grange_holford_guentert_2001_complete____main() // Sub-modules, and any changes to those submodules: environment: grange_holford_guentert_2001_complete__environment(time_); gastrointestinal_compartment_L_dopa: grange_holford_guentert_2001_complete__gastrointestinal_compartment_L_dopa(F_c_dopa, A_dopa_c, ka_c_dopa, CL_dopa_0, time_); body_compartment_L_dopa: grange_holford_guentert_2001_complete__body_compartment_L_dopa(C_dopa_c, time_, A_dopa_c, F_c_dopa, ka_c_dopa, CL_dopa); body_compartment_3_OMD: grange_holford_guentert_2001_complete__body_compartment_3_OMD(time_, C_dopa_c, CL_COMT); L_dopa_clearance: grange_holford_guentert_2001_complete__L_dopa_clearance(CL_dopa, CL_dopa_0, CL_COMT, C_Ro_central); gastrointestinal_compartment_benserazide: grange_holford_guentert_2001_complete__gastrointestinal_compartment_benserazide(A_bens, ka_B, F_B, time_); central_compartment_benserazide: grange_holford_guentert_2001_complete__central_compartment_benserazide(C_bens_central, CLd_B, time_, A_bens, ka_B, F_B, C_bens_peripheral, CL_bens_total); peripheral_compartment_benserazide: grange_holford_guentert_2001_complete__peripheral_compartment_benserazide(C_bens_peripheral, time_, CLd_B, C_bens_central); benserazide_clearance: grange_holford_guentert_2001_complete__benserazide_clearance(CL_bens_total, CL_Ro); gastrointestinal_compartment_Ro: grange_holford_guentert_2001_complete__gastrointestinal_compartment_Ro(A_Ro, ka_M, F_Ro, time_); central_compartment_Ro: grange_holford_guentert_2001_complete__central_compartment_Ro(C_Ro_central, CLd_M, time_, C_bens_central, CL_Ro, A_Ro, ka_M, F_Ro, C_Ro_peripheral); peripheral_compartment_Ro: grange_holford_guentert_2001_complete__peripheral_compartment_Ro(C_Ro_peripheral, time_, CLd_M, C_Ro_central); end