Hi, I would like to build a model to describe a circadian rhythm. Basically I assume that the release rate is linearly increasing from Tmin to Tmax, and linearly decreasing from Tmax to Tmin in 24 hr period. My code is as follows (I tried to put integer operation in $DES, to convert every time point after 24hr to 0-24hr period). My run failed at the covariance step, and nonmem gave me a warning: (WARNING 68) THE INTEGER FUNCTION IS BEING USED OUTSIDE OF A SIMULATION BLOCK. IF THE INTEGER VALUE AFFECTS THE VALUE OF THE OBJECTIVE FUNCTION, THEN AN ERROR WILL PROBABLY OCCUR. How the warning will affect my nonmem output? Why the run failed? Any suggestions on the coding will be highly appreciated. Thank you.
Best wishes, lili NONMEM CODE: ;PD Model KOUT = 0.4 ;Elimination rate constant (1/hr) RMAX = THETA(1)*EXP(ETA(1)) ;Maximum release rate (ng/ml/hr) TMIN = THETA(2)*EXP(ETA(2)) ;Time at minimum release rate (hr) TGAP = THETA(3)*EXP(ETA(3)) ;Time from minimum rate to maximum release rate (hr) BSL = THETA(4)*EXP(ETA(4)) ;Concentration at time zero (ng/ml) SD = THETA(5) ;CV% of residual TMAX = TMIN+TGAP A_0(1) = BSL $DES T1= T-24*INT(T/24) ;Convert time to 0-24 period, the MOD function is not working in NONMEM IF (T1.LE.TMIN) THEN ;Make the time start from Tmin T2=T1+24 ELSE T2=T1 ENDIF IF (T2.LE.TMAX) THEN KIN=RMAX*(T2-TMIN)/TGAP ELSE KIN=RMAX*(TMIN+24-T2)/(24-TGAP) ENDIF DADT(1)= KIN-KOUT*A(1) $ERROR IPRED=F Y=F*(1+SD*EPS(1)) IRES=DV-IPRED IWRES=IRES/SD/F
