A question based approach to drug development
Visser, S.J. de
Citation
Visser, S. J. de. (2003, September 10). A question based approach to drug development.
Retrieved from https://hdl.handle.net/1887/28222
Version:
Corrected Publisher’s Version
License:
Licence agreement concerning inclusion of doctoral thesis in the
Institutional Repository of the University of Leiden
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Cover Page
The handle
http://hdl.handle.net/1887/28222
holds various files of this Leiden University
dissertation
Author: Visser. Samuel Jacob de
A question based
approach to drug
development
p r o e f s c h r i f t
ter verkrijging van de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus Dr.D.D.Breimer, hoogleraar in de faculteit der Wiskunde
en Natuurwetenschappen en die der Geneeskunde, volgens besluit van het College voor
Promoties te verdedigen op woensdag 10 september 2003 te klokke 14:15 uur door
p r o m o t i e c o m m i s s i e
p r o m o t o r
Prof. Dr A.F. Cohen
c o p r o m o t o r e s
Dr J.M.A. van Gerven
Dr B. Tuk, Tuk Management b.v.
r e f e r e n t
Prof. Dr J. Urquhart, Maastricht University & ucsf, San Fransisco, usa
o v e r i g e l e d e n
Prof. Dr E. Uchida, Showa University, Tokyo, Japan
Prof. Dr M. Danhof
Prof. Dr E.C. Klasen
The printing of this thesis was financially supported by the foundation ‘Centre for Human Drug Research’, Leiden, The Netherlands
c o n t e n t s
i n t r o d u c t i o n
p a g e 8 1. Drug development project management by a new question based approach and decision analysis support
s e c t i o n 1
p a g e 30 2. Biomarkers for the effects of antipsychotic drugs in healthy volunteers p a g e 56 3. Biomarkers for the effects of benzodiazepines in healthy volunteer
p a g e 78 4. rem sleep effects as a biomarker for the effects of antidepressants in healthy volunteers p a g e 96 t h e va l u e o f r e s e a r c h o n b i o m a r k e r s
s e c t i o n 2
p a g e 110 5. Comparison of an oral solution and an oral sustained release formulation of rilmenidine in eight healthy volunteers and correlation with in vitro sustained release properties p a g e 126 6. Concentration-effect relationships of two infusion rates of the imidazoline
antihypertensive agent rilmenidine for blood pressure and development of side-effects in healthy subjects
p a g e 140 7. Concentration-effect relationships of two rilmenidine single-dose infusion rates in hypertensive patients
p a g e 158 8. Pharmacokinetic/pharmacodynamic assessment of tolerance to central nervous system effects of a 3 mg sustained release tablet of rilmenidine in hypertensive patients
p a g e 174 t h e va l u e o f t i m i n g a d d i t i o n a l s t u d i e s
s e c t i o n 3
p a g e 182 9. Pharmacodynamics and pharmacokinetics of a single oral dose of nitrazepam in healthy male and female volunteers. An interethnic comparative study between Japanese and Caucasian volunteers
p a g e 198 10. Pharmacokinetic differences between Caucasian and Japanese subjects after single and multiple doses of a potential combined oral contraceptive (Org 30659 and ee)
p a g e 214 a d d e d va l u e o f b r i d g i n g s t u d i e s
s e c t i o n 4
p a g e 224 11. Pharmacodynamic and pharmacokinetic effects of mrla023, a gabaa12,3subtype selective agonist, compared to lorazepam and placebo in healthy volunteers
p a g e 240 t h e va l u e o f d e t e r m i n i n g c r i t i c a l q u e s t i o n s e a r ly
