[LONGITUDINAL]

input = {D50, f1, Tmax_1, dTmax_2, CV_1, CV_2, V, k21, k12, kmet, ke}

EQUATION:

pi = 3.14159265358979

;dose-dependent first-pass effect

Fr = amtDose/(amtDose + D50)

Tmax_3 = Tmax_1

CV_3 = CV_1

;inverse gaussian distribution absorption

MAT_1 = Tmax_1/(sqrt(1+9/4*(CV_1^4))-3/2*(CV_1^2))

MAT_2 = (Tmax_1+dTmax_2)/(sqrt(1+9/4*(CV_2^4))-3/2*(CV_2^2))

MAT_3 = Tmax_3/(sqrt(1+9/4*(CV_3^4))-3/2*(CV_3^2))

inv_gauss_1 = Fr*amtDose*f1*sqrt(MAT_1/(2*pi*(CV_1^2)*(t^3)))*exp(-((t-MAT_1)^2)/(2*(CV_1^2)*MAT_1*t))

inv_gauss_2 = Fr*amtDose*(1-f1)*sqrt(MAT_2/(2*pi*(CV_2^2)*(t^3)))*exp(-((t-MAT_2)^2)/(2*(CV_2^2)*MAT_2*t))

inv_gauss_3 = (1-Fr)*amtDose*sqrt(MAT_3/(2*pi*(CV_3^2)*(t^3)))*exp(-((t-MAT_3)^2)/(2*(CV_3^2)*MAT_3*t))

;ODE

if t < tDose

dArosco = 0

else

dArosco = inv_gauss_1 + inv_gauss_2 - kmet*Arosco + k21*Aroscop - k12*Arosco

dAroscop = k12*Arosco - k21*Aroscop

end

if t < tDose

dAM3 = 0

else

dAM3 = kmet*Arosco + inv_gauss_3 − ke*AM3

end

ddt_Arosco = dArosco

ddt_Aroscop = dAroscop

ddt_AM3 = dAM3

;V/F in litres

C_rosco = Arosco/V*1000

C_M3 = AM3/V*1000

;AUC

AUC_rosco_0 = 0

ddt_AUC_rosco = C_rosco

AUC_M3_0 = 0

ddt_AUC_M3 = C_M3

OUTPUT:

output = {C_rosco, C_M3}