DESCRIPTION:
PD = Friberg et al (2002) 'Model of Chemotherapy-Induced Myelosuppression with Parameter Consistency Across Drugs', Journal of Clinical Oncology 20:4713-4721

[LONGITUDINAL]
input = {ka, V, Cl, Circ0, MTT, gam, Emax, EC50}
; ka = {use=regressor}
; V  = {use=regressor}
; Cl = {use=regressor}

EQUATION:

; PK model
Cc = pkmodel(ka, V, Cl)

; parameter transformations
n = 3
ktr = (n+1)/MTT
kprol = ktr
kcirc = ktr

; drug effect
Edrug = Emax * Cc/(EC50 + Cc)

; initial values
t_0 = 0
Prol_0 = Circ0
T1_0 = Circ0
T2_0 = Circ0
T3_0 = Circ0
Circ_0 = Circ0

;ODEs for the response
ddt_Prol = kprol*Prol*(1-Edrug)*(Circ0/Circ)^gam - ktr*Prol
ddt_T1 = ktr*Prol - ktr*T1
ddt_T2= ktr*T1 - ktr*T2
ddt_T3 = ktr*T2 - ktr*T3
ddt_Circ = ktr*T3 - kcirc*Circ

OUTPUT:
output = {Cc, Circ}