Transcript
Page 1: The innovative medicines initiative IMI—A new collaborative approach to drug safety testing and beyond

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Abstracts / Toxicology L

djust the dosing schedule, according to the needs and responsesf patients under treatment.

oi:10.1016/j.toxlet.2009.06.395

27evelopment and validation of a nonaqueous capillary elec-

rophoresis method for the quantification of donepezil inuman plasma

iriana Gubandru ∗, Dan Balalau, Mihaela Ilie, Carmen Purdel

UMF Carol Davila, Toxicology, Bucharest, Romania

he bioavailability and non-compliance to treatment withonepezil represent major issues, mainly in clinical trials anddjusting dose settings, so frequently drug-level measurement is aesirable tool to improve clinical outcomes with Alzheimer drugs.

A simple, rapid and sensitive procedure using nonaqueous cap-llary electrophoresis (NACE) to measure donepezil levels has beeneveloped and validated.

Optimum detection of donepezil was obtained at 315 nm, using64.5 cm (56 to the detector) × 50 �m i.d. fused-silica capillary. Theonaqueous mobile phase consisted in 15 mM ammonium acetate

n methanol–acetonitrile (7:3, v/v), the operating voltage was set at5 kV. Injection was performed in the hydrodynamic mode (0.5 psi,0 s). In these conditions, the peak of donepezil was obtained at4.41 ± 0.15 min.

The calibration curve was linear in the range of 0.5–5 �g/mLR2 > 0.992). Intra/interday accuracy and precision were found to beess than 10% and 5%, respectively, at three control concentrationevels.

The results obtained prove that the NACE method is suitable toonitor plasma levels of donepezil and can properly be used to

ssess patient’s compliance to medication.

oi:10.1016/j.toxlet.2009.06.396

28he neuroprotective effects of progesterone on experimentaliabetic neuropathy in rats

arzieh Panahi ∗, Mohammadreza Sameni

Jundishapour Ahwaz University, Anatomical Sciences, Ahwaz, Islamicepublic of Iran

iabetic neuropathy is one of the most common complicationsffecting more than 50–60% of diabetic patients and it is a commonause of non-traumatic amputation and autonomic failure. Neu-oactive steroids, such as progesterone (PROG), have been recentlydentified as promising neuroprotective agents in several modelsf neurodegeneration. In this study we investigated the potentialeuroprotective effect of PROG in experimental model of diabeticeuropathy. Animals were randomly divided into 3 groups (with 10ats in each), control (nondiabetic), untreated diabetic and diabeticROG-treated. Diabetes was induced in adult male rats by a singleose injection of streptozotocin (STZ, 55 mg kg−1, i.p.). In the PROG-reated group, 4 weeks after induce of diabetes; rats were treated

ith PROG (8 mg kg−1, i.p., every 2 days) for 6 weeks. Diabetic rats

howed a significant reduction in motor nerve conduction velocityMNCV), mean myelinated fibers (MFs) diameter, axon diameternd myelin sheath thickness in the sciatic nerve after 6 weeks.n the untreated diabetic group endoneurial edema was observed

tosp

189S (2009) S57–S273 S265

n sciatic nerve and the numbers of MFs with infolding into thexoplasm, irregularity of fibers, myelin sheath with unclear bound-ries and alteration in myelin compaction were also increased.ong-term treatment with PROG increased MNCV significantly andrevented all these abnormalities in treated diabetic rats. Ourndings indicated that PROG as a therapeutic approach can pro-ect neurophysiologic and histomorphologic alterations induced byeripheral diabetic neuropathy.

eywords: Progesterone; Sciatic nerve; Diabetic neuropathy; Nerveonduction velocity; Histomorphometry

oi:10.1016/j.toxlet.2009.06.397

29he innovative medicines initiative IMI—A new collaborativepproach to drug safety testing and beyond

atthias Gottwald

Bayer Schering Pharma AG, Global Drug Discovery Operations -xternal R&D Policy, Berlin, Germany

espite huge spendings in pharmaceutical R&D, the attrition ratef drug development projects is still at an unacceptable high levelith limited safety and/or efficacy of the tested compounds beingajor reasons. Validated methods for an early reliable prediction

f safety and efficacy of new medicines are urgently needed.In 2004 the idea for a new collaborative approach was born to

ddress these issues via a new public–private-partnership model,qually funded by the European Commission and the Europeanederation of Pharmaceutical Industries and Associations EFPIA.ogether with all stakeholders a research agenda has been devel-ped which sets the frame for annual rounds of big collaborativerojects, bringing together experts from many pharmaceuticalompanies, academia, SMEs, patient organisations and publicuthorities.

In 2008 the first call for proposal within IMI has been publishedith several topics in the area of safety prediction. The new collab-

rative approach of IMI and an overview on the first projects anduture plans will be presented.

Selected for Oral Presentation.

oi:10.1016/j.toxlet.2009.06.398

30epatoprotective and antioxidant activity of phytic acid and/oratechin against carbon tetrachloride-induced hepatotoxicity inats

ohair Hassan 1,∗, Maha Zaki Rizk 1, Fathia El-Sharkawi 2, Osamaadary 3, Mai Osman Kadry 3

Advanced Dental and Medical Institute, Biochemistry, Pinang, Egypt,Helwan University, Biochemistry Department, Helwan, Egypt, 3 Ainhams University, Clinical Pharmacy Department, Ain Shams, Egypt

n this study, the rat model of carbon tetrachloride (CCl4)-inducedepatotoxicity was used to assess the effect of daily intraperi-

oneal injections of catechin, phytic acid and their combinationn the indices of cirrhosis. Liver enzymes profiling, oxidativetatus and histological examinations revealed that catechin andhytic acid significantly arrested progression of hepatic cirrho-

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