 Newsletter CHDR Summer 2010
Wanted: Interns
The student training at CHDR is open to any student with a (bio-) medical/ scientific background. The training program primarily aims to teach knowledge, learn skills and applications of state-of-the-art methodology in human drug studies. It provides a unique opportunity to get insight in the intriguing process of drug or method development. In addition, the CHDR provides a board-certified education program in clinical pharmacology that is open for trainees.
To apply for a training period at the CHDR, please contact us.
Trials and techniques
 PK model in Plasma and Saliva
As blood sampling is undesirable in children in the setting of a non-therapeutic study, saliva samples are a suitable alternative to measure the drug concentration. By combining these data with pharmacokinetic data in blood, a PK model can be build that provides us with estimated plasma drug levels in children needed for population PK/PD analysis. A randomized, open-label study has been performed to elucidate pharmacokinetic plasma and saliva profiles and to describe the relationship between plasma and saliva concentrations and use for the analysis of data obtained in children.
Lenneke Schrier
PK and PD efficacy in women with sexual dysfunction
In collaboration with the sexology departments of the AMC and LUMC, CHDR will perform a study in women with sexual dysfunction. The study will investigate the PK profile and preliminary PD efficacy of a novel treatment administration route. During this 3-day in-patient study, patients will receive the study drug twice daily and PK profiles will be obtained after single and repeated dosing. Efficacy will be measured using validated computer tests, psychophysiologic measures such as vaginal pulse amplitude and measures of subjective experience using questionnaires. Considering the high prevalence of sexual dysfunction in women and unmet need of effective pharmacotherapeutic options, the drug under investigation may provide a solution for this often overlooked problem.
Helene van Gorsel
Presentations, Publications and Posters
 WorldPharma
Come and visit us at the WorldPharma congress in Copenhagen, July 17-23.
Abstracts
- Effects of caffeine on central and autonomous nervous system parameters in adolescents (oral), Koos Burggraaf et al
- Whole blood challenge tests as translational tools for early assessment of anti-inflammatory/ immunosuppressive effects of drugs (poster), Andrea Kales et al
- The effect of olanzapine on THC induced psychomimetic symptoms (poster), Kleinloog D. et al
- Modulation of vasoactivity and platelet aggregation by 5-HT antagonism (poster), Matthijs Moerland et al
- Evaluation of the EndoPAT as a tool to assess endothelial function (poster), Matthijs Moerland et al
- Evaluation of a glucagon challenge test as a tool in diabetes research (poster), Marloes van Dongen et al
- Pharmacological resting state fMRI study using THC (poster), Linda Klumpers et al
 CINP
Our visit to the CINP conference June 6-10 in Hong Kong was a large success. CHDR was the most publishing output unit of the 3500 participants. Please find the overview and downloads of our posters here.
First Proof of Pharmacology of a Novel Glucagon Receptor Antisense Drug in Humans
Morgan es, Brandt TA, van Dongen MGJ, Geerts BF, Burggraaf J, Romijn, JA, Cohen , AF, Watanage TA, Geary RS, Bhanot S
ADA Scientific Sessions, Abstract, 2010.
The reduction of hepatic glucagon receptor (GCGR) expression with antisense oligonucleotides (ASO) was tested in a SAD and MAD design in healthy subjects. The subjects underwent a glucagon-challenge procedure at baseline and at the end of treatment to determine the pharmacological efficacy. The ASO treatment significantly blunted both the glucagon-induced increase in plasma glucose and hepatic glucose and showed a consistent PK-PD relationship with preclinical data. In conclusion, the results support further evaluation of the GCGR antisense approach in patients with T2DM.
Sputum induction with hypertonic saline reduces fractional exhaled nitric oxide in chronic smokers and non-smokers.
Zuiker RG, Boot JD, Calderon C, Piantone A, Petty K, de Kam M, Diamant Z.
Respir Med. 2010; 104: 917-920
The objective of the study was to evaluate the reproducibility and differences in fractional exhaled NO (FeNO) values in asymptomatic chronic smokers and healthy, non-smoking controls and to test the effect of hypertonic saline sputum induction on FeNO levels in both study groups. Our data extend previous findings in asthmatics and healthy controls to asymptomatic chronic smokers.
 Measurement of collagen- and serotonin-induced platelet aggregation in whole blood
Moerland M, Kemme MJ, van der Linden M and Burggraaf J
Expert Rev. Clin. Pharmacol. 2010; 3: 177-182
Upon erosion and rupture of an atherosclerotic plaque, collagen and serotonin (5-HT) induce a process of simultaneous platelet aggregation and vasoconstriction. We developed and validated a method using impedance aggregometry, which is feasible to measure 5-HT-induced platelet aggregation in whole blood for the evaluation of promising platelet aggregation inhibitors possessing 5-HT antagonistic activity.
Method development studies for repeatedly measuring anxiolytic drug effects in healthy humans.
Klumpers F, van Gerven JM, Prinssen EP, Roche IN, Roesch F, Riedel WJ, Kenemans JL, Baas JM.
J Psychopharmacol. 2010; 24: 657-666
A threat-of-shock paradigm and adaptations of the Trier mental arithmetic test and the Stroop colour naming test were tested whether they are suitable for human experimental models for anxiety. The anxiety responses to this test battery were evaluated whether they remain stable after repeated testing and whether the paradigm is suitable for a crossover design with multiple sessions. It is concluded that especially the startle paradigm could be a useful new instrument for screening new anxiolytic drugs.
Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant
 Hoever P, de Haas S, Winkler J, Schoemaker RC, Chiossi E, van Gerven J, Dingemanse J.
Clin Pharmacol Ther. 2010; 87: 593-600.
Almorexant, a potentially representing a new class of sleep-promoting compounds, was administered in an ascending single-dose study to evaluate tolerability, PK and PD. 7 cohorts of 10 healthy male subjects were enrolled to test different dose levels. Population PK/PD modeling suggested that doses of ~500 mg almorexant and 10 mg zolpidem are equivalent with respect to subjectively assessed alertness.
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