incorporate lag time in ADVAN 6

Hi, I have concentration data from 4 clinical trials and one of those might have a lag time. A nonlinear model was used to fit the data. So I need to incorporate lag time into the differential equations. Does anybody know how to do this? Many thanks in advance. Best, Kehua

I suggest you to go to the html folder, open index.htm and look at "absorption lag parameter". Usually the tlag is in the absorption compartment (most often defined as compartment 1).Therefore ALAG1 is a reserved variable that will create a delay (ALAG1) in the dose input time (in compartment 1). For example ALAG1=THETA(1)*DEXP(ETA(1)) code inserted in the PK block will result in the estimation of both the fixed and random effect for that reserved variable ALAG1 (through THETA(1) and ETA(1)). Serge Guzy; Ph.D President, CEO; POP_PHARM; INC; www.poppharm.com USAGE: $PK ALAG1= .... DISCUSSION: Absorption lag parameters are used with PREDPP. They are optional additional PK parameters. With NM-TRAN, they are symbolized in the $PK block by reserved variables ALAGn, where n is the compartment num- ber to which the parameter applies. There is one absorption lag time (parameter) associated with every possible dose compartment of the kinetic model (the output compartment is not a possible dose compartment) and the absorption lag time used for a given dose is that one associated with the compartment into which the dose is given (the dose compartment). The event time t on a dose record refers to the recorded time the dose was administered. In the case of a regular infusion, t is the time the infusion was initiated. An absorption lag time is an increment of time L such that the time that the dose is regarded (by PREDPP) as entering (or starting to enter) the system is t+L. Absorption lag times are optional in the sense that absorption lag times associated with compartments never used as dose compartments may be ignored. The values of absorption lag times that are not computed in PK are always understood to be 0. An absorption lag time for a dose is computed by the PK routine using, if needed, information in the dose record. When additional doses are specified on a dose event record, the absorption lag time applies to the dose and to all the additional doses. With a steady-state multi- ple dose the absorption lag time applies not only to this dose, but also to all the preceding implied doses. With a steady-state dose, the lag time should be less than the interdose interval.