Predictions beyond SS dosing time + II

All, I've recently been working up a Phase 2 PK data set: oral administration, QD dosing and PK samples on weeks 3, 5 and 7 of the study. Per protocol, the morning dose is withheld and the patient comes to the clinic for a blood sample. To me, this seems like a straightforward application of SS and II, something like: ID DATE TIME CMT DV EVID AMT SS II MDV 11101 3/30/2010 7:45 1 . 1 200 1 24 1 11101 3/31/2010 9:33 2 25.6 0 . . . 0 However, Guide V, section 8.2.8 indicates predictions can't be made beyond the dosing time + II: "Ordinarily, steady-state levels can only be predicted between t1 , the time on the steady-state dose record, and t2 , the sum of t1 and the interdose interval. If it is not only necessary to compute a steady-state prediction between t1 and t2 , but also after t2 , then there must also occur one or more non-steady-state dose records at t2 , t2+II , etc. with doses just like the steady-state dose. " Here, the PK sample is taken after dosing + II. NONMEM 7.1.2 appears to give me a prediction, but I'm suspicious of the results. I thought about adding a very, very small transient dose at the II, but the language in 8.2.8 seems to indicate the dose needs be "just like the steady-state dose", so that might not work. * Have others encountered this issue, and if so, what did you do to work around the limitation? * Can other shed some light on what predictions can't be made beyond II, since transient equations can be mixed with SS equations? Warm Regards, Mike Dodds