Mats O. Karlsson, Niclas Jonsson, Gunnar Nyberg* and Janet R. Wade
Dept of Pharmacy, Div. of Pharmacokinetics, Box 580, Uppsala University, Uppsala, Sweden, *Dept of Clinical Pharmacology, Astra Hassle, Gothenburg, Sweden
Data from 10 separate studies (4 experimental studies in volunteers (n=50) and 6 observational studies in patients (n=142)) who received 5-isosorbidemononitrate (Imdur) were combined and analysed using the. first-order method in NONMEM.
Methods
- A flexible, staircase, input model was used.
- Simplified model building using empirical Bayes estimates was employed (1).
- Case deletion diagnostics were used to identify the dependence of the final model on the ten different studies.
Results
- The characterized in vivo absorption profile was found to be very similar to the in vitrodissoultion profile.
- The volume in volunteers was found to be 25% higher than that in the patients.
- A previously unrecognized 40% lower clearance with concomitant beta-blocker therapy was found.
1) Mandema et al., J. Pharm. Biopharm. 18:511-528 (1992).
Reference: PAGE 2 () Abstr 917 [www.page-meeting.org/?abstract=917]
Poster: oral presentation