Is the use of II, SS, and ADDL allowed simultaneously

Dear NMusers, Is the use of II, SS, and ADDL allowed simultaneously in NONMEM? I wish to assess PK profiles at SS with and without compliance. Here is the potential scenario I am interested in: i) Patients come in at SS and take their 1st two doses correctly ii) Patients then remain compliant OR miss a dose OR ingest a double dose iii) Patients then resume taking their doses correctly For (i) I will need II, SS and ADDL For (ii) I don't need any II or SS or ADDL For (iii) I will need II and ADDL Kindly advice...Mahesh PS. I am aware that I can hard code (formatting via S-plus etc) each dose after the first SS dose as a separate dosing record but I wish to know if there is an easier method available

Hi Mahesh, For compliant patients, you may use ADDL, II and SS simultaneously. Assuming you have same dose type (dose, II) for additional doses. For non-compliant patients who skipped the dose(s), I would add dose event record(s) after you the steady state dosing. For non-compliant patients who doubled the dose(s), then you may use SS=2. The following is an example I found from Sheiner's training material which took place ~10 years ago. TIME AMT RATE SS II 50 20 . 0 . 64 10 . 2 8 a 10 mg bolus dose every 8 hrs, steady-state at 64 hrs, superimposed on a 20 mg bolus dose at 50 hours. I hope this helps. Joseph Joseph Kim, Ph.D., RPh. Principal Clinical Pharmacokineticist CPK/Modelling & Simulation GlaxoSmithKline Research Triangle Park North Carolina 27709 U.S.A. "Samtani, Mahesh [PRDUS]" <[EMAIL PROTECTED]> Sent by: [EMAIL PROTECTED] 02-Jan-2008 12:43 To [email protected] cc Subject [NMusers] Is the use of II, SS, and ADDL allowed simultaneously Dear NMusers, Is the use of II, SS, and ADDL allowed simultaneously in NONMEM? I wish to assess PK profiles at SS with and without compliance. Here is the potential scenario I am interested in: i) Patients come in at SS and take their 1st two doses correctly ii) Patients then remain compliant OR miss a dose OR ingest a double dose iii) Patients then resume taking their doses correctly For (i) I will need II, SS and ADDL For (ii) I don?t need any II or SS or ADDL For (iii) I will need II and ADDL Kindly advice?Mahesh PS. I am aware that I can hard code (formatting via S-plus etc) each dose after the first SS dose as a separate dosing record but I wish to know if there is an easier method available

There are a number of examples on combining Steady State with transient doses in NONMEM Users Guide V "Introductory", Chapter 6 Section 8.2.8. Combining Non-Steady-State Doses with Steady-State Doses. In general, you can use SS dose event if there is a regular, repeated pattern of dosing. But if patients who were at Steady state then have irregular patterns of doses, then you will need "hard coded" doses to describe the actual doses. Once a patient is assumed to be at SS again, then a record with SS=1 could be used to reset the drug level back to steady state. On Wed, 2 Jan 2008 14:21:40 -0500, [EMAIL PROTECTED] said: > Hi Mahesh, > > For compliant patients, you may use ADDL, II and SS simultaneously. > Assuming you have same dose type (dose, II) for additional doses. For > non-compliant patients who skipped the dose(s), I would add dose event > record(s) after you the steady state dosing. For non-compliant > patients who doubled the dose(s), then you may use SS=2. > > The following is an example I found from Sheiner's training material > which took place ~10 years ago. > > TIME AMT RATE SS II 50 20 . 0 > . 64 10 . 2 8 > > > a 10 mg bolus dose every 8 hrs, steady-state at 64 hrs, superimposed > on a 20 mg bolus dose at 50 hours. > > > I hope this helps. > > > Joseph > > Joseph Kim, Ph.D., RPh. Principal Clinical Pharmacokineticist > CPK/Modelling & Simulation GlaxoSmithKline Research Triangle Park > North Carolina 27709 U.S.A. > > > > > > > > > "Samtani, Mahesh [PRDUS]" <[EMAIL PROTECTED]> Sent by: owner- > [email protected] 02-Jan-2008 12:43 > > > To [email protected] cc > > Subject [NMusers] Is the use of II, SS, and ADDL allowed > simultaneously > > > > > > > Dear NMusers, Is the use of II, SS, and ADDL allowed simultaneously in > NONMEM? I wish to assess PK profiles at SS with and without > compliance. Here is the potential scenario I am interested in: > i) Patients come in at SS and take their 1st two doses correctly > ii) Patients then remain compliant OR miss a dose OR ingest a double > dose > iii) Patients then resume taking their doses correctly For (i) I will > need II, SS and ADDL For (ii) I don?t need any II or SS or ADDL > For (iii) I will need II and ADDL Kindly advice?Mahesh > PS. I am aware that I can hard code (formatting via S-plus etc) each > dose after the first SS dose as a separate dosing record but I > wish to know if there is an easier method available > -- Alison Boeckmann [EMAIL PROTECTED]