Hi, We got the data from our steady state pilot study for an immediate release formulation and prolong formulation. Volunteers received a multiple-dose of IR (twice a day) and prolong formulation (once a day) during 14 days. On day 14, blood samples were drawn (48 hours) after drug administration: volunteers received IR formulation twice and prolong formulation once a day. So we got two data set of plasma concentration vs time: for IR formulation with two peaks and for prolong formulation. Can I use NCA to get PK parameters of both formulations? Is Tau 14 days or 48 hours? How can I compare two peaks plasma profile of IR formulation with a prolong formulation peak? Thank you, Helen
Helen, TAU is the dosing interval. So for your IR (twice a day) it is 12 HOURS and for your prolong formulation (once a day) 24 HOURS You need to specify the time of last dose to NCA so for the IR, depending how you formatted your data this may be 12 hours so you look at just that last dose-event profile. Your second question I am not so sure about - “can I compare two peaks plasma profile of IR formulation with a prolong formulation peak?” the peaks will of course be smaller for the more frequent but smaller IR doses but perhaps you should compare Cavg etc. to see if you’ve obtained similar SS levels Simon.
Simon, thank you very much for your prompt answer. Right now I am dealing with steady-state study methodology. I have to compare steady-state pharmacokinetics of controlled release and immediate release formulations. I do it at first time, so I have some problems. Is it correct to compare plasma profiles in my case? Or IR formulation should be administrated once a day in the day of taking blood samples? I am very grateful you for any example. Helen
Hi Helen, your setup is quite common. You developed a CR release formulation in order to improve compliance, etc. You should compare AUCs within 24 hours. I would calculate two partial AUCs of the IR dataset: 0-12 and 12-24. Compare the sum of these to AUCtau of the CR dataset. Cmax is another story. If your CR mimics the IR (eg. is a pulsatile formulation) filter both datasets for 0-12 and 12-24 and run two NCAs to get the two peaks. Compare them separatelly. If your CR shows a single peak (or a flat profile) compare this one to the global Cmax of the IR dataset (within 0-24).
Helmut, thank you very much for your help.
Hi Helmut! I’d like to ask you to suggest me Pharmacokinetic books that can help in my case. Thank you, Helen
Hi Helen, the comparison of two IR doses to a single MR dose is standard – though not specifically stated in regulatory guidelines. 
Maybe helpful: W Cawello (Ed.) Parameters for Compartment-Free Pharmacokinetics. Standardisation of Study Design, Data Analysis and Reporting Shaker-Verlag, Aachen 2003, ISBN 3-8265-4767-5 D Hauschke, V Steinijans and I Pigeot Bioequivalence Studies in Drug Development. Methods and Applications John Wiley, Chichester 2007, ISBN 978-0-470-09475-4
Helmut thank you very much. I’ll try it definitely