#benson1



#reactions
absorp:
 {1.0}PFM_gut = {1.0}PFM_p
  kabs_PFM * MD
dist:
 {1.0}PFM_p = {1.0}PFM_r
  kout_PFM * PFM_p - kin_PFM * PFM_r
elim:
 {1.0}PFM_p = $pool
  klinear_PFM * PFM_p + Vm_PFM * PFM_p / (Km_PFM + PFM_p / Vss_PFM) / Vss_PFM
vA_UE_b:
 {1.0}A_b = $pool
  BRAIN * b_FAAH_Brain * kcl_A * A_b
vA_UE_r:
 {1.0}A_r = $pool
  c_NAAA_ROB * kcl_A * A_r
vA_b_m:
 {1.0}A_b = {1.0}A_m
  MEC * ktr_m_p_A * (A_b - A_m) / (A_m + A_b + Km_p_m_A)
vA_degr_b:
 {1.0}A_b = $pool
  BRAIN * FAAH_b * kcat_FAAH * a_FAAH_A * A_b / (Km_FAAH_A * FAAH_D_b)
vA_degr_m:
 {1.0}A_m = $pool
  MEC * FAAH_m * kcat_FAAH * a_FAAH_A * A_m / (Km_FAAH_A * FAAH_D_m)
vA_degr_r:
 {1.0}A_r = $pool
  ROB * FAAH_r * kcat_FAAH * a_FAAH_A * A_r / (Km_FAAH_A * FAAH_D_r)
vA_m_p:
 {1.0}A_m = {1.0}A_p
  MEC * ktr_m_p_A * (A_m - A_p * Ktr_p_m_A) / (A_m + A_p + Km_p_m_A)
vA_r_p:
 {1.0}A_r = {1.0}A_p
  PLASMA * ktr_r_p * (A_r - A_p * Ktr_p_r_A) / (A_r + A_p + Km_p_m_A)
vA_syn_b:
 {1.0}NAPE_b = {1.0}A_b
  BRAIN * PLD_b * k_NA_PE * NAPE_b / Km_NA_PE / den_b
vA_syn_r:
 {1.0}NAPE_r = {1.0}A_r
  ROB * PLD_r * k_NA_PE * NAPE_r / Km_NA_PE / den_r
vFAAH_degr_b:
 {1.0}FAAH_b = $pool
  BRAIN * k_deg_FAAH * FAAH_b
vFAAH_degr_m:
 {1.0}FAAH_m = $pool
  MEC * k_deg_FAAH * FAAH_m
vFAAH_degr_r:
 {1.0}FAAH_r = $pool
  ROB * k_deg_FAAH * FAAH_r
vFAAH_inh_b:
 {1.0}FAAH_b = {1.0}FAAHinh_b
  BRAIN * k_inh * FAAH_b * PF_b
vFAAH_inh_degr_b:
 {1.0}FAAHinh_b = $pool
  BRAIN * k_deg_FAAH * FAAHinh_b
vFAAH_inh_degr_m:
 {1.0}FAAHinh_m = $pool
  MEC * k_deg_FAAH * FAAHinh_m
vFAAH_inh_degr_r:
 {1.0}FAAHinh_r = $pool
  ROB * k_deg_FAAH * FAAHinh_r
vFAAH_inh_m:
 {1.0}FAAH_m = {1.0}FAAHinh_m
  MEC * k_inh * FAAH_m * PF_m
vFAAH_inh_r:
 {1.0}FAAH_r = {1.0}FAAHinh_r
  ROB * k_inh * FAAH_r * PF_r
vFAAH_syn_b:
 $pool = {1.0}FAAH_b
  BRAIN * FAAH_t * b_FAAH_Brain * k_deg_FAAH
vFAAH_syn_m:
 $pool = {1.0}FAAH_m
  MEC * FAAH_t * b_FAAH_MEC * k_deg_FAAH
vFAAH_syn_r:
 $pool = {1.0}FAAH_r
  FAAH_t * c_FAAH_ROB * k_deg_FAAH
vL_UE_b:
 {1.0}L_b = $pool
  BRAIN * b_FAAH_Brain * kcl_L * L_b
vL_UE_r:
 {1.0}L_r = $pool
  c_NAAA_ROB * kcl_L * L_r
vL_b_m:
 {1.0}L_b = {1.0}L_m
  MEC * ktr_m_p_L * (L_b - L_m)
vL_degr_b:
 {1.0}L_b = $pool
  BRAIN * FAAH_b * kcat_FAAH * a_FAAH_L * L_b / (Km_FAAH_L * FAAH_D_b)
vL_degr_m:
 {1.0}L_m = $pool
  MEC * FAAH_m * kcat_FAAH * a_FAAH_L * L_m / (Km_FAAH_L * FAAH_D_m)
vL_degr_r:
 {1.0}L_r = $pool
  ROB * FAAH_r * kcat_FAAH * a_FAAH_L * L_r / (Km_FAAH_L * FAAH_D_r)
vL_m_p:
 {1.0}L_m = {1.0}L_p
  MEC * ktr_m_p_L * (L_m - L_p * Ktr_p_m_L)
vL_r_p:
 {1.0}L_r = {1.0}L_p
  PLASMA * ktr_r_p * (L_r - L_p * Ktr_p_r_L)
vL_syn_b:
 {1.0}NLPE_b = {1.0}L_b
  BRAIN * PLD_b * k_NL_PE * NLPE_b / Km_NL_PE / den_b
vL_syn_r:
 {1.0}NLPE_r = {1.0}L_r
  ROB * PLD_r * k_NL_PE * NLPE_r / Km_NL_PE / den_r
vNAPE_syn_b:
 $pool = {1.0}NAPE_b
  BRAIN * Vmax_NAT * p_A * a_NAT_A * b_NAT_Brain
vNAPE_syn_r:
 $pool = {1.0}NAPE_r
  Vmax_NAT * p_A * a_NAT_A * c_NAT_ROB
vNLPE_syn_b:
 $pool = {1.0}NLPE_b
  BRAIN * Vmax_NAT * p_L * a_NAT_L * b_NAT_Brain
vNLPE_syn_r:
 $pool = {1.0}NLPE_r
  Vmax_NAT * p_L * a_NAT_L * c_NAT_ROB
vNOPE_syn_b:
 $pool = {1.0}NOPE_b
  BRAIN * Vmax_NAT * p_O * a_NAT_O * b_NAT_Brain
vNOPE_syn_r:
 $pool = {1.0}NOPE_r
  Vmax_NAT * p_O * a_NAT_O * c_NAT_ROB
vNPPE_syn_b:
 $pool = {1.0}NPPE_b
  BRAIN * Vmax_NAT * p_P * a_NAT_P * b_NAT_Brain
vNPPE_syn_r:
 $pool = {1.0}NPPE_r
  Vmax_NAT * p_P * a_NAT_P * c_NAT_ROB
vNSPE_syn_b:
 $pool = {1.0}NSPE_b
  BRAIN * Vmax_NAT * p_S * a_NAT_S * b_NAT_Brain
vNSPE_syn_r:
 $pool = {1.0}NSPE_r
  Vmax_NAT * p_S * a_NAT_S * c_NAT_ROB
vO_UE_b:
 {1.0}O_b = $pool
  BRAIN * b_FAAH_Brain * kcl_O * O_b
vO_UE_r:
 {1.0}O_r = $pool
  c_NAAA_ROB * kcl_O * O_r
vO_b_m:
 {1.0}O_b = {1.0}O_m
  MEC * ktr_m_p_O * (O_b - O_m)
vO_degr_b:
 {1.0}O_b = $pool
  BRAIN * FAAH_b * kcat_FAAH * a_FAAH_O * O_b / (Km_FAAH_O * FAAH_D_b)
vO_degr_m:
 {1.0}O_m = $pool
  MEC * FAAH_m * kcat_FAAH * a_FAAH_O * O_m / (Km_FAAH_O * FAAH_D_m)
vO_degr_r:
 {1.0}O_r = $pool
  ROB * FAAH_r * kcat_FAAH * a_FAAH_O * O_r / (Km_FAAH_O * FAAH_D_r)
vO_r_p:
 {1.0}O_r = {1.0}O_p
  PLASMA * ktr_r_p * (O_r - O_p * Ktr_p_r_O)
vO_syn_b:
 {1.0}NOPE_b = {1.0}O_b
  BRAIN * PLD_b * k_NO_PE * NOPE_b / Km_NO_PE / den_b
vO_syn_r:
 {1.0}NOPE_r = {1.0}O_r
  ROB * PLD_r * k_NO_PE * NOPE_r / Km_NO_PE / den_r
vP_UE_b:
 {1.0}P_b = $pool
  BRAIN * b_FAAH_Brain * kcl_P * P_b
vP_UE_r:
 {1.0}P_r = $pool
  c_NAAA_ROB * kcl_P * P_r
vP_b_m:
 {1.0}P_b = {1.0}P_m
  MEC * ktr_m_p_P * (P_b - P_m)
vP_degr_b:
 {1.0}P_b = $pool
  BRAIN * FAAH_b * kcat_FAAH * a_FAAH_P * P_b / (Km_FAAH_P * FAAH_D_b)
vP_degr_m:
 {1.0}P_m = $pool
  MEC * FAAH_m * kcat_FAAH * a_FAAH_P * P_m / (Km_FAAH_P * FAAH_D_m)
vP_degr_r:
 {1.0}P_r = $pool
  ROB * FAAH_r * kcat_FAAH * a_FAAH_P * P_r / (Km_FAAH_P * FAAH_D_r)
vP_m_p:
 {1.0}P_m = {1.0}P_p
  MEC * ktr_m_p_P * (P_m - P_p * Ktr_p_m_P)
vP_r_p:
 {1.0}P_r = {1.0}P_p
  PLASMA * ktr_r_p * (P_r - P_p * Ktr_p_r_P)
vP_syn_b:
 {1.0}NPPE_b = {1.0}P_b
  BRAIN * PLD_b * k_NP_PE * NPPE_b / Km_NP_PE / den_b
vP_syn_r:
 {1.0}NPPE_r = {1.0}P_r
  ROB * PLD_r * k_NP_PE * NPPE_r / Km_NP_PE / den_r
vS_UE_b:
 {1.0}S_b = $pool
  BRAIN * b_FAAH_Brain * kcl_S * S_b
vS_UE_r:
 {1.0}S_r = $pool
  c_NAAA_ROB * kcl_S * S_r
vS_b_m:
 {1.0}S_b = {1.0}S_m
  MEC * ktr_m_p_S * (S_b - S_m)
vS_degr_b:
 {1.0}S_b = $pool
  BRAIN * FAAH_b * kcat_FAAH * a_FAAH_S * S_b / (Km_FAAH_S * FAAH_D_b)
vS_degr_m:
 {1.0}S_m = $pool
  MEC * FAAH_m * kcat_FAAH * a_FAAH_S * S_m / (Km_FAAH_S * FAAH_D_m)
vS_degr_r:
 {1.0}S_r = $pool
  ROB * FAAH_r * kcat_FAAH * a_FAAH_S * S_r / (Km_FAAH_S * FAAH_D_r)
vS_m_p:
 {1.0}S_m = {1.0}S_p
  MEC * ktr_m_p_S * (S_m - S_p * Ktr_p_m_S)
vS_r_p:
 {1.0}S_r = {1.0}S_p
  PLASMA * ktr_r_p * (S_r - S_p * Ktr_p_r_S)
vS_syn_b:
 {1.0}NSPE_b = {1.0}S_b
  BRAIN * PLD_b * k_NS_PE * NSPE_b / Km_NS_PE / den_b
vS_syn_r:
 {1.0}NSPE_r = {1.0}S_r
  ROB * PLD_r * k_NS_PE * NSPE_r / Km_NS_PE / den_r
vo_m_p:
 {1.0}O_m = {1.0}O_p
  MEC * ktr_m_p_O * (O_m - O_p * Ktr_p_m_O)


#parameters
AG2_b = 0.0
Dose = 10.0
ED50 = 0.53
Emax_PFM = 0.773
FAAH_t = 78.0
Gut = 1.65
H = 0.48
Heart = 0.31
Kd_AG2 = 3424.0
Kd_CB1_A = 239.2
Ki_A = 230.0
Ki_L = 1000.0
Ki_O = 240.0
Ki_P = 6700.0
Ki_S = 840.0
Kidney = 0.28
Km_FAAH_A = 8200.0
Km_FAAH_L = 10800.0
Km_FAAH_O = 52200.0
Km_FAAH_P = 543000.0
Km_FAAH_S = 10000.0
Km_NA_PE = 2800.0
Km_NL_PE = 1000.0
Km_NO_PE = 2900.0
Km_NP_PE = 3300.0
Km_NS_PE = 3400.0
Km_PFM = 26.1
Km_p_m_A = 1.0
Kp_b_PF = 1.3
Kp_m_PF = 1.3
Kp_r_PF = 1.5
Ktr_p_m_A = 1.89
Ktr_p_m_L = 2.77
Ktr_p_m_O = 9.07
Ktr_p_m_P = 2.65
Ktr_p_m_S = 30.01
Ktr_p_r_A = 0.62
Ktr_p_r_L = 0.89
Ktr_p_r_O = 2.8
Ktr_p_r_P = 0.85
Ktr_p_r_S = 9.19
LEU = 0.025
LIVER = 1.69
Leucocytes = 0.025
Lungs = 1.172
M_A = 347.5
M_L = 323.5
M_O = 325.5
M_P = 299.5
M_PF = 455.4
M_S = 321.5
Muscles = 35.0
PLD_b = 10000000.0
PLD_r = 10000000.0
Pancreas = 0.077
R_PF = 0.6
Spleen = 0.192
Testis = 0.036
Thymus = 0.029
Vm_PFM = 1511.0
Vmax_NAT = 300.0
Vss_PFM = 58.328
a_FAAH_A = 1.0
a_FAAH_L = 1.15
a_FAAH_O = 5.7
a_FAAH_P = 37.8
a_FAAH_S = 1.0
a_NAT_A = 1.0
a_NAT_L = 8.6
a_NAT_O = 13.0
a_NAT_P = 0.42
a_NAT_S = 1.0
b_FAAH_Brain = 0.197
b_FAAH_Gut = 0.034
b_FAAH_Kidney = 0.069
b_FAAH_Leucocytes = 0.0
b_FAAH_Liver = 1.0
b_FAAH_Lungs = 0.032
b_FAAH_MEC = 0.137
b_FAAH_Spleen = 0.03
b_FAAH_Testis = 0.126
b_NAAA_Brain = 0.6
b_NAAA_Gut = 0.2
b_NAAA_Heart = 0.2
b_NAAA_Kidney = 0.6
b_NAAA_Liver = 1.0
b_NAAA_Lungs = 14.0
b_NAAA_Spleen = 8.0
b_NAAA_Testis = 0.6
b_NAAA_Thymus = 4.0
b_NAT_Brain = 1.667
b_NAT_Heart = 1.0
b_NAT_Kidney = 0.667
b_NAT_Leucocytes = 0.0
b_NAT_Lungs = 0.033
b_NAT_Muscles = 0.333
b_NAT_Pancreas = 0.333
b_NAT_Testis = 0.667
e1 = 0.0
k_NA_PE = 202.0
k_NL_PE = 100.0
k_NO_PE = 230.0
k_NP_PE = 270.0
k_NS_PE = 280.0
k_deg_FAAH = 0.0051
k_inh = 1.1
kabs_PFM = 2.2
kcat_FAAH = 18000.0
kcl_A = 1.74
kcl_L = 1.25
kcl_O = 2.5
kcl_P = 2.61
kcl_S = 1.2
kin_PFM = 0.117
klinear_PFM = 0.0803
kout_PFM = 0.18
ktr_m_p_A = 150.0
ktr_m_p_L = 0.0
ktr_m_p_O = 10.0
ktr_m_p_P = 10.0
ktr_m_p_S = 10.0
ktr_r_p = 100.0
p_A = 0.051
p_L = 0.016
p_O = 0.098
p_P = 0.615
p_S = 0.191
t = 0.0
BRAIN = 1.45000004768372
Default = 1.0
MEC = 1.49999996210681e-05
PLASMA = 2.6489999294281
ROB = 65.3000030517578


#initial values
A_b = 0.7493309
A_m = 0.97761
A_p = 0.8740574
A_r = 0.5419204
FAAH_b = 15.366
FAAH_m = 10.686
FAAH_r = 2.165868
FAAHinh_b = 0.0
FAAHinh_m = 0.0
FAAHinh_r = 0.0
L_b = 2.319571
L_m = 0.0
L_p = 1.916254
L_r = 1.705466
NAPE_b = 3.879041e-05
NAPE_r = 4.241633e-06
NLPE_b = 7.550331e-05
NLPE_r = 8.256095e-06
NOPE_b = 0.0008814287
NOPE_r = 9.638198e-05
NPPE_b = 0.0001732296
NPPE_r = 1.894222e-05
NSPE_b = 0.0001272629
NSPE_r = 1.391587e-05
O_b = 20.77858
O_m = 16.3219
O_p = 5.085073
O_r = 14.23822
PFM_gut = 0.0
PFM_p = 0.0
PFM_r = 0.0
P_b = 6.541209
P_m = 5.809415
P_p = 4.849307
P_r = 4.121915
S_b = 3.427807
S_m = 2.968774
S_p = 0.273772
S_r = 2.515968


#assignment rules
!F tid = t / 2.400000e+01
!F CB1_b = (A_b / Kd_CB1_A + AG2_b / Kd_AG2) / (1.000000e+00 + A_b / Kd_CB1_A + AG2_b / Kd_AG2)
!F SG_p = 1.000000e-03 * S_p * M_S
!F LG_p = 1.000000e-03 * L_p * M_L
!F PG_p = 1.000000e-03 * P_p * M_P
!F PFG_p = 1.000000e-03 * PFM_p / Vss_PFM
!F F_r = 1.500000e+03 * FAAH_r / (FAAHinh_r + FAAH_r)
!F FAAH_D_b = 1.000000e+00 + A_b / Km_FAAH_A + O_b / Km_FAAH_O + P_b / Km_FAAH_P + L_b / Km_FAAH_L + S_b / Km_FAAH_S
!F PF_m = PF_p * Kp_m_PF
!F PF_r = PF_p * Kp_r_PF
!F den_b = 1.000000e+00 + slag1_b + slag2_b
!F MD = PFM_gut + 1.000000e+06 * Dose * F_PFM
!F PF_b = PF_p * Kp_b_PF
!F FAAH_D_r = 1.000000e+00 + A_r / Km_FAAH_A + O_r / Km_FAAH_O + P_r / Km_FAAH_P + L_r / Km_FAAH_L + S_r / Km_FAAH_S
!F den_r = 1.000000e+00 + slag1_r + slag2_r
!F c_FAAH_ROB = LIVER * b_FAAH_Liver + Gut * b_FAAH_Gut + Spleen * b_FAAH_Spleen + Kidney * b_FAAH_Kidney + Lungs * b_FAAH_Lungs + Testis * b_FAAH_Testis + Leucocytes * b_FAAH_Leucocytes
!F AG_p = 1.000000e-03 * A_p * M_A
!F OG_p = 1.000000e-03 * O_p * M_O
!F FAAH_D_m = 1.000000e+00 + A_m / Km_FAAH_A + O_m / Km_FAAH_O + P_m / Km_FAAH_P + L_m / Km_FAAH_L + S_m / Km_FAAH_S
!F c_NAAA_ROB = LIVER * b_NAAA_Liver + Gut * b_NAAA_Gut + Spleen * b_NAAA_Spleen + Kidney * b_NAAA_Kidney + Heart * b_NAAA_Heart + Lungs * b_NAAA_Lungs + Thymus * b_NAAA_Thymus + Testis * b_NAAA_Thymus * Testis
!F slag2_r = A_r / Ki_A + O_r / Ki_O + P_r / Ki_P + L_r / Ki_L + S_r / Ki_S
!F slag1_r = NAPE_r / Km_NA_PE + NOPE_r / Km_NO_PE + NPPE_r / Km_NP_PE + NLPE_r / Km_NL_PE + NSPE_r / Km_NS_PE
!F c_NAT_ROB = Pancreas * b_NAT_Pancreas + Kidney * b_NAT_Kidney + Heart * b_NAT_Heart + Lungs * b_NAT_Lungs + Muscles * b_NAT_Muscles + Testis * b_NAT_Testis + Leucocytes * b_NAT_Leucocytes
!F slag2_b = A_b / Ki_A + O_b / Ki_O + P_b / Ki_P + L_b / Ki_L + S_b / Ki_S
!F slag1_b = NAPE_b / Km_NA_PE + NOPE_b / Km_NO_PE + NPPE_b / Km_NP_PE + NLPE_b / Km_NL_PE + NSPE_b / Km_NS_PE
!F PF_p = 1.000000e+00 / M_PF * PFM_p / Vss_PFM
!F F_PFM = Emax_PFM * Dose / (ED50 + Dose)