When modeling plasma concentrations after oral administration there can be a lagtime for the drug appearing in the plasma. One has the option of using a 1 cpt model , V, first order absorption and elimination with a lag time. This can work very well, but if the lag is pronounced the model may not fit the early plasma concentrations well ( lag time zone) while fitting the rest of the profile.
I have written very simple models along the lines of published work that include a series of lag time compartments and they work well for fitting single doses of drug. The lagtime zone plus the rest ofthe profile is fitted well.
An example of code for single dose would be below. CON (1) = dose
The single dose plasma concentrations are fitted well.
I am now considering how I can include simulating for multiple doses in the code. That way I could predict plasma concentrations after say 5 doses.
So how would I approach including the option to simulate (predict) say 5 doses of drug once a day for example using the fitting of the single dose paranaters.
NCON=1
NFUNCTIONS 1
NDERIVATIVES 8
NPARAMETERS 9
NSEC 2
PNAMES 'K01','KLAG','KLAG2','KLAG3','KLAG4', 'KLAG5','KLAG6', 'K10','V_F'
SNAMES 'AUC','K10_hl',
END
1: TEMPORARY
2: V1=P(9)
3: END
4: START
5: Z(1) = CON(1)
6: Z(2) = 0
7: Z(3) = 0
8: Z(4) = 0
9: Z(5) = 0
10: Z(6) = 0
11: Z(7)= 0
12: Z(8)= 0
13: END
14: DIFFERENTIAL
15: DZ(1) = -K01*Z(1)
16: DZ(2) = K01*Z(1)-KLAG*Z(2)
17: DZ(3) = KLAG*Z(2)-KLAG2*Z(3)
18: DZ(4) = KLAG2*Z(3)-KLAG3*Z(4)
19: DZ(5) = KLAG3*Z(4)-KLAG4*Z(5)
20: DZ(6)= KLAG4*Z(5)-KLAG5*Z(6)
21: DZ(7)= KLAG5*Z(6)-KLAG6*Z(7)
22: DZ(8)= KLAG6*Z(7)-K10*Z(8)
23: END
24: FUNCTION 1
25: F =Z(8)/V_F
26: END
27: SECO
28: D=CON(1)
29: AUC=D/P(9)/K10
30: K10_HL=-DLOG(0.5)/K10
31: END
32: EOM
Do you have any suggestions
angus