Dr. Jean-Paul Tillement
Member

EDUCATION
1959 : Pharmacist, Faculté de Pharmacie de Paris, France.
1960 : Bachelor of Sciences, Faculté des Sciences de Paris, France.
1968 : Doctorate of Medecine (MD), Faculté de Médecine de Paris, France.

ACADEMIC APPOINTMENTS
1963-1965 Attaché-assistant de Pharmacologie, Faculté de Médecine de Paris (Pr. Jean CHEYMOL)
1965-1968 Attaché-assistant de Pharmacologie, Faculté de Médecine de Paris (Pr. Jacques-Robert BOISSIER)
1971 Maître de Conférences Agrégé de Pharmacologie, Faculté de Médecine de Paris XII
1983 Professeur sans chaire à la Faculté de Médecine de Paris XII (Professor of Pharmacology)
1985-today Professeur titulaire de Pharmacologie à la Faculté de Médecine de Paris XII (Professor of Pharmacology with tenure; Head of the Department of Pharmacology)

HOSPITAL APPOINTMENTS
1958 Interne en Pharmacie des Hopitaux de Paris (Resident)
1962 Assistant de Biologie des Hopitaux (Assistant)
1971 Biologiste des Hopitaux de Paris (Qualified Biologist)
1979 Chef de Service Hospitalier de Pharmacologie (Head of the Department of Clinical Pharmacology)

NATIONAL APPOINTMENTS
1977-1988 Member of the "Commission Nationale de Pharmacovigilance", French Ministry of Health
1979-today Expert auprès du Ministère de la Santé, French Ministry of Health
1984-today Expert judiciaire près de la Cour d'Appel de Paris, French Ministry of Justice
1986-1990 Vice-Président de la Commission Spécialisée n° 2 de l'INSERM (Commission de Pharmacologie Fondamentale et Clinique)

OTHER - Involvement in the COST project, Brussels (Belgium), «Criteria for the choice and definition of healthy volunteers and or patients for phase I and II studies in drug development".

EDITORIAL APPOINTMENTS
- Member of the Editorial Board of the following journals :
. Clinical Pharmacokinetics
. Drugs
. European Journal of Drug Metabolism and Pharmacokinetics
. Fundamental and Clinical Pharmacology
. International Journal of Clinical Pharmacology Research
. International Journal of Clinical Pharmacology and Therapeutics
. Pharmacological Research
. Therapeutic Drug Monitoring
. Thérapie
- Reviewer for the following journals:
. Archives Internationales de Pharmacodynamie et de Thérapie
. Biochemical Pharmacology
. Journal of Pharmaceutical Sciences
. Journal of Pharmacy and Pharmacology
. European Journal of Clinical Pharmacology
. Biochimica et Biophysica Acta

PROFESSIONAL SOCIETIES
- Past Président of the «Société Française de Pharmacologie Clinique et de Thérapeutique»
- Member of the «Association Française des Pharmacologistes»
- Member of the «Société Nationale de Médecine Interne»
- Member of the «Société de Psychiatrie Biologique»
- Member of the «Société Européenne de Pneumologie»
- Member of the «European Society of Biochemical Pharmacology»
- Member of the «American Heart Association»
- Member of the «Collegium Internationale Neuropsychopharmacologicum»
- Member of the «Mediterranean Society of Clinical Pharmacology»
- Member of the «American Society for Clinical Pharmacology and Therapeutics»
- Member of the «Société Française de Pharmacologie»

HONORS AND AWARDS
1969 Lauréat de l'Académie Nationale de Médecine : Prix Charles Helme.
1982 Chevalier dans l'Ordre des Palmes Académiques.
1983 Médaille de l'Académie Nationale de Pharmacie, Médaille J.B. Dumas.
1990 Officier dans l'Ordre des Palmes Académiques.
1990 Distinction de la Société Japonaise de Pharmacologie (Tokyo).
1991 Docteur Honoris Causa de l'Université de Lausanne (Switzerland).
1997 Election à l'Académie Nationale de Pharmacie (Member of the National Academy of Pharmacy).

FIELDS OF INTEREST My position allows me to undertake three different but complementary tasks: cure of patients, teaching and research. The team that I lead involves 20 scientists, that include medical doctors, pharmacists, senior scientists, postdoctoral fellows, predoctoral students and undergraduate students. Our specific subjects of interest are found in three tasks.

Clinical pharmacokinetics
Our original works deal with the pharmacological significance of drug-protein interaction and especially with plasma proteins. We showed that the plasma binding of a drug is not always relevant in the sense it does not systematically lead pharmacokinetic parameters. The relevance is observed only when plasma binding of a drug retains it in the distribution space of its binding protein. This case is observed when the overall binding capacity of the protein expressed as n.ka (where n is the number of binding sites and ka the corresponding association constant) is higher than that of tissues and / or organs of the body. Then the drug is sequestered totally or partly, in the compartment of its binding protein. Thus binding percentages of drugs in plasma have a limited interest as they cannot indicate if their corresponding binding capacities are higher or lower than these of tissues. In order to understand the possible role of the plasma binding, it has to be referred to the apparent volume of distribution of the drug (Vd). If its value is less than that of exchangeable water 0.6 l.kg-1, it is probable that plasma binding impairs a total distribution of the drug into the body. Thus, we have proposed to name "restrictive plasma binding" such situations where drugs are poorly (quantitatively) distributed in tissues. NSAIDs are classical examples of such distribution where high binding percentages (> 95%) in plasma to HSA are associated with a small Vd, approximately 0.1 l.kg-1 which volume is both equal and superimposable (data from autoradiographies) with the Vd of HSA. On the contrary, some plasma bindings sometimes including high binding percentages (> 95%) are named "permissive" when they do not induce any significant retention process. Such drugs exhibit high Vd, virtuals (apparents) higher than that of exchangeable water (0.6 l.kg-1) Common examples are given by psychotropic drugs. For instance, Vd of 4 l.kg-1 indicates that the corresponding drug enters cells and is bound inside (for these drugs, in brain). We used this concept for drug monitoring of highly bound drugs in plasma exhibiting a low Vd i.e. a restrictive binding. In this situation, monitoring may use adequately the free drug concentration in plasma instead of the overall concentration (valproic acid).

Experimental and clinical neuropsychopharmacology
I was trained in experimental pharmacology in the laboratory of the psychiatric clinics of Sainte-Anne hospital (Paris), the heads of which were Professors DELAY and DENIKER, discoverers of the mental effects of chlorpromazine. My teacher was Professor BOISSIER. Within his group, we developed various tests in order to predict possible clinical effects of various substances. These tests included animal behaviour evaluation and biochemical assays. I developed assays of cerebral biogenic amines, receptor binding studies in order to identify targets of drugs and in the various steps of neurotransmitters synthesis, release and reuptake. Now this experimental research is stopped and I concentrate my interest on the next topic. However I keep a great interest for progress in this field and I share it with former students, now psychiatrists with whom we settled educational sessions of critical analysis of new data involving drugs, pathophysiologies of mental diseases and selected therapies. I have the responsibility of supplying a part of their internet site devoted to new drugs of this field (www.fmcdpsy.org) .

Pharmacological preservation of mitochondrial functions
This research is devoted to the only acquired mitochondrial diseases. It involves the patients whose mitochondrial functions are normal at birth but will be altered during life by various insults, oxidative stresses, cellular degeneration (especially neuronal), acute or chronic ischemia associated or not with reperfusion, or, more simply, cellular ageing.

Three main functions of mitochondria are considered, ATP synthesis i.e. the integrity of oxidative phosphorylation, the limitation of the generation of ROS enough to destroy pathogenic agents but quantitatively limited in order to avoid lipoperoxidation of cellular membranes and Ca2+ storage regulation inside mitochondrial matrix. We have shown that cyclosporin A induced nephrotoxicity is not only due to vasoconstriction it develops which obviously decreases oxygen rates of the cells. This drug promotes also a cellular hypoxia, easily assessed in normoxia, which is the consequence of Ca2+ accumulation inside the mitochondrial matrix. As a result, ATP synthesis is decreased which is one determinant of chronic renal insufficiency. This observation is supported by the fact that vasodilators do not counteract chronic cyclosporine A induced nephrotoxicity. It is possible to counteract this evolving hypoxia with an anti-ischemic drug, trimetazidine, used also in angor but effective upon renal ischemia. Its main interests are its safety and the fact it does not modify the immunosuppressant effects of cyclosporin A. Moreover we were able to show that trimetazidine can prevent or limit ischemia induced damages using other models evidencing that its anti-ischemic effect is general and not linked to cyclosporin A. The first model we used is the in vivo liver ischemia followed by reperfusion in the rat. Trimetazidine has a preventive effect, which involves an increase of survivals, a better and quicker restoration of hepatic functions and in cells, a preservation of mitochondrial functions. These effects are dose dependent. Then the second step involved humans. Selected patients were a scribed to a hydatic kyst removal. When pretreated with trimetazidine, the time needed for the recovery of hepatic functions was shortened. Another experimental model was to check trimetazidine for graft storage and preservation bath (UW). It was observed that added drug ameliorated the quality of the graft and favored its functional recovery (rat and pig). Further studies are now running. All these data have prompted us to propose the following hypothesis. It is possible to limit the alterations promoted by the sequences of ischemia followed by reperfusion by administrating drugs before the sequence. So it preserves cellular mitochondrial functions. Thus the proposed concept is to induce a cytoprotection by a previous administration of drugs which stabilize mitochondrial functions, ATP synthesis, ROS generations, Ca2+ homeostasis inside the mitochondrial matrix, before the ischemic sequence. A retrospective study is now done in order to know if various drugs which anti-ischemic and / or antioxidants effects are assessed, develop also mitochondrial effects. Surprisingly we have observed that E-resveratrol, an antioxidant, inhibits also ROS generation from complex III and limits the intensity of lipoperoxidation of cellular membranes. These data are in accordance with the benefit of the moderate absorption of red wine (resveratrol is inside the skin of grapes) which decreases the number and the intensity of cardiac diseases (infartus) and central neurologic ones (dementia) after 65 years of age. Other authors demonstrated that drugs mainly used in angor, amiodarone perhexiline, have mitochondrial effects. They decrease the amount of fatty acids to be oxidized and increase the amount of glucose, which brings a higher yield of energy. Mitochondrial targets of some drugs or nutriments are shown on figure N°1. Some of them are potentially interesting for the preservation of mitochondrial functions: they represent new fields of research. The last example evidences the role of mitochondrial ATP in the effectiveness and in the safety of a drug, namely Zidovudine (ZDV or AZT). This agent inhibits and / or kills HIV. It is a prodrug and as such inactive. The active form is the triphosphorylated derivative which is generated with mitochondrial ATP. The monophosphorylated one, ZDV-P, is both inactive upon HIV and toxic for the cells and especially upon mitochondria (loss of impermeability of mitochondrial internal membrane and swelling as a consequence). This fact explains why in some patients, ZDV may loose its efficiency and becomes toxic (increase of lactic acid generation). The treatment is either to restore ATP synthesis, or to protect it by a preventive treatment. Trimetazidine is a optional candidate but its interest is not yet assessed.

PUBLICATIONS My scientific work includes more than 540 publications (May, 2001) consisting of Research & Educational Papers, Reviews & Books, Communications & Posters, Direction of Doctoral Theses (30). Only the list of publications since 1998 is presented below.

Original publications since 1998

1998

1 ROLE OF LIPOPROTEINS IN THE PLASMA BINDING OF SDZ PSC 833, A NOVEL MULTIDRUG RESISTANCE-REVERSING CYCLOSPORIN N. SIMON, E. DAILLY, O. COMBES, E. MALAURIE, M. LEMAIRE, JP TILLEMENT & S. URIEN Br. J. Clin. Pharmacol. 1998, 45, 173-175.

2 THE GENETIC VARIANT A OF HUMAN ALPHA 1-ACID GLYCOPROTEIN LIMITS THE BLOOD TO BRAIN TRANSFER OF DRUGS IT BINDS P. JOLLIET-RIANT, M.F. BOUKEF, J-C. DUCHE, N. SIMON, J-P. TILLEMENT Life Sci., 1998, 62 (14), PL219-226. Pharmacology Letters

3 EVIDENCE FOR THE EXISTENCE OF 3H-TRIMETAZIDINE BINDING SITES INVOLVED IN THE REGULATION OF THE MITOCHONDRIAL PERMEABILITY TRANSITION PORE D. MORIN, A. ELIMADI, R. SAPENA, A. CREVAT, P-A. CARRUPT, B. TESTA and J-P. TILLEMENT Br. J. Pharmacol., 1998, 123, 1385-1394.

4 CHAIN-BREAKING ANTIOXIDANTS AND FERRIHEME-BOUND DRUGS ARE SYNERGISTIC INHIBITORS OF ERYTHROCYTE MEMBRANE PEROXIDATION E. DAILLY, S. URIEN and J-P. TILLEMENT Free Rad. Res., 1998, 28, 205-214.

5 MOLECULAR PROPERTIES AND PHARMACOKINETIC BEHAVIOR OF CETIRIZINE, A ZWITTERIONIC H1-RECEPTOR ANTAGONIST A. PAGLIARA, B. TESTA, P-A. CARRUPT, P. JOLLIET, C. MORIN, D. MORIN, S. URIEN, J-P. TILLEMENT and J-P. RIHOUX J. Med. Chem., 1998, 41, 853-863.

6 EVIDENCE FOR THE STABILISATION OF THE HIGH-AFFINITY STATE OF BETA-ADRENOCEPTORS BY AN ENDOGENOUS FACTOR IN RAT BRAIN V. GARNIER, R. ZINI, D. MORIN and J-P. TILLEMENT Pharmacological Research, 1998, 37(5), 365-373.

7 STRUCTURE-PROPERTY RELATIONSHIPS OF TRIMETAZIDINE DERIVATIVES AND MODEL COMPOUNDS AS POTENTIAL ANTIOXIDANTS J. ANCEREWICZ, E. MIGLIAVACCA, P-A. CARRUPT, B. TESTA, F. BREE, R. ZINI, J-P. TILLEMENT, S. LABIDALLE, D. GUYOT, A-M. CHAUVET-MONGES, A. CREVAT and A. LE RIDANT Free Radical Biology & Medicine, 1998, 25(1), 113-120.

8 TACROLIMUS DECREASES IN VITRO OXIDATIVE PHOSPHORYLATION OF MITOCHONDRIA FROM RAT FOREBRAIN R. ZINI, N. SIMON, C. MORIN, L. THIAULT and J-P. TILLEMENT Life Sci., 1998, 63(5), 357-368.

9 EFFECTS OF TRIMETAZIDINE ON LIPID PEROXIDATION AND PHOSPHORUS METABOLITES DURING COLD STORAGE AND REPERFUSION OF ISOLATED PERFUSED RAT KIDNEYS T. HAUET, G. BAUZA, JM. GOUJON, JC. CARITEZ, M. CARRETIER, M. EUGENE and JP. TILLEMENT J. Pharmacol. Exp. Ther., 1998, 285(3), 1061-1067.

10 TRIMETAZIDINE COUNTERACTS THE HEPATIC INJURY ASSOCIATED WITH ISCHEMIA-REPERFUSION BY PRESERVING MITOCHONDRIAL FUNCTION A. ELIMADI, A. SETTAF, D. MORIN, R. SAPENA, F. LAMCHOURI, Y. CHERRAH and J-P. TILLEMENT J. Pharmacol. Exp. Ther., 1998, 286(1), 23-28.

11 ROLE OF BILIRUBIN IN THE REGULATION OF THE TOTAL PEROXYL RADICAL TRAPPING ANTIOXIDANT ACTIVITY OF PLASMA IN SICKLE CELL DISEASE E. DAILLY, S. URIEN, J. BARRE, Ph. REINERT and J-P. TILLEMENT Biochem. Biophys. Res. Commun., 1998, 248, 303-306.

12 LIGAND SPECIFICITY OF THE GENETIC VARIANTS OF HUMAN ALPHA1-ACID-GLYCOPROTEIN : GENERATION OF A THREE-DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP MODEL FOR DRUG BINDING TO THE A VARIANT. F. HERVE, G. CARON, J-C. DUCHE, P. GAILLARD, N.A. RAHMAN, A. TSANTILI-KAKOULIDOU, P.A. CARRUPT, P. D'ATHIS, J-P. TILLEMENT and B. TESTA. Mol. Pharmacol., 1998, 54, 129-138.

13 PLASMA COENZYME Q10 CONCENTRATIONS IN BREAST CANCER : PROGNOSIS AND THERAPEUTIC CONSEQUENCES P. JOLLIET, N. SIMON, J. BARRE, J-Y. PONS, M. BOUKEF, B-J. PANIEL and J-P TILLEMENT Int. J. Clin. Pharmacol. Ther., 1998, 36(9), 506-509.

14 DOSE-RELATED INVERSION OF CINNARIZINE AND FLUNARIZINE EFFECTS ON MITOCHONDRIAL PERMEABILITY TRANSITION A. ELIMADI, L. BOUILLOT, R. SAPENA, J-P. TILLEMENT and D. MORIN Eur. J. Pharmacol., 1998, 348, 115-121.

15 GLUCOCORTICOIDS DECREASE CYTOCHROME C OXIDASE ACTIVITY OF ISOLATED RAT KIDNEY MITOCHONDRIA N. SIMON, P. JOLLIET, C. MORIN, R. ZINI, S. URIEN and J-P. TILLEMENT FEBS Letters, 1998, 435, 25-28.

16 STUDY OF THE EXPRESSION OF THE GENETIC VARIANTS OF HUMAN ALPHA-1-ACID GLYCOPROTEIN IN HEALTHY SUBJECTS USING ISOELECTRIC FOCUSING AND IMMUNOBLOTTING J-C. DUCHE, F. HERVE, J-P. TILLEMENT J. Chromatogr., 1998, 715, 103-109.

17 EFFICIENCY OF TRIMETAZIDINE IN RENAL DYSFUNCTION SECONDARY TO COLD ISCHEMIA-REPERFUSION INJURY : A PROPOSED ADDITION TO UNIVERSITY OF WINSCONSIN SOLUTION T. HAUET, C. TALLINEAU, J-M. GOUJON, M. CARRETIER, M. EUGENE and J-P TILLEMENT Cryobiology, 1998, 37, 231-244.

18 TRIMETAZIDINE REVERSES DELETERIOUS EFFECTS OF ISCHEMIA-REPERFUSION IN THE ISOLATED PERFUSED PIG KIDNEY MODEL T. HAUET, D. MOTHES, J-M. GOUJON, T. GERMONVILLE, J-C. CARITEZ, M. CARRETIER, M. EUGENE, J-P TILLEMENT Nephron, 1998, 80, 296-304.

1999

1 TRIMETAZIDINE AMELIORATES THE HEPATIC INJURY ASSOCIATED WITH ISCHAEMIA-REPERFUSION IN RATS A. SETTAF, D. MORIN, F. LAMCHOURI, A. ELIMADI, Y. CHERRAH and J-P. TILLEMENT Pharmacological Research, 1999, 39 (3), 211-216

2 A GppNHp-INSENSITIVITY FACTOR MODULATES THE ACTIVATION OF BETA-ADRENOCEPTOR-COUPLED Gs PROTEIN IN RAT CORTEX AND CEREBELIUM V. GARNIER, R. ZINI, J-P. TILLEMENT Fundam. Clin. Pharmacol., 1999, 13, 169-179. 3 TRIMETAZIDINE AMELIORATES THE HEPATIC INJURY ASSOCIATED WITH ISCHAEMIA-REPERFUSION IN RATS A. SETTAF, D. MORIN, F. LAMCHOURI, A. ELIMADI, Y. CHERRAH and J-P. TILLEMENT Pharmacological Research, 1999, 39(3), 211-216.

4 EFFECTS OF RESVERATROL ON THE RAT BRAIN RESPIRATORY CHAIN R. ZINI, C. MORIN, A. BERTELLI, A.A.E. BERTELLI, J-P. TILLEMENT Drugs Exptl. Clin. Res., 1999, XXV(2/3), 87-97.

5 THE pH-PARTITION PROFILE OF THE ANTI-ISCHEMIC DRUG TRIMETAZIDINE MAY EXPLAIN ITS REDUCTION OF INTRACELLULAR ACIDOSIS F. REYMOND, G. STEYAERT, J-A. CARRUPT, D. MORIN, J-P. TILLEMENT, H. H. GIRAULT and B. TESTA Pharmaceutical Research, 1999, 16(5), 616-624.

6 RENOPROTECTIVE EFFECTS OF TRIMETAZIDINE AGAINST ISCHEMIA- REPERFUSION INJURY AND COLD STORAGE PRESERVATION : A PRELIMINARY STUDY H. BAUMERT, J-M. GOUJON, J-P. RICHER, L. LACOSTE, J-P. TILLEMENT, M. EUGENE, M. CARRETIER and T. HAUET Transplantation, 1999, 68(2), 300-303.

7 A PHARMACOKINETIC-PHARMACODYNAMIC MODELLING OF THE ANTIHISTAMINIC (H1) EFFECTS OF CETIRIZINE S. URIEN, J-P. TILLEMENT, B. GANEM and M-D. DUCH Inter. J. Clin. Pharmacol. Ther, 1999, 37(10), 499-502.

8 SYMPATHOMIMETIC EFFECTS OF PARQUETINA NIGRESCENS (PERIPLOCACEAE) EXTRACT IN ISOLATED PORTAL VEIN SMOOTH MUSCLE J.Y. DATTE, A. ZIEGLER and J-P. TILLEMENT General Pharmacology, 1999, 32, 551-556.

9 MEDICAMENTS INTERAGISSANT AVEC LES MITOCHONDRIES : EFFETS ANTI-ISCHEMIQUES DE LA TRIMETAZIDINE M. SPEDDING, J-P. TILLEMENT, D. MORIN, A. LE RIDANT Thérapie, 1999, 54(5), 627-635.

2000

1 PHARMACOLOGICAL LIMITATION OF DAMAGE TO RENAL MEDULLA AFTER COLD STORAGE AND TRANSPLANTATION BY TRIMETAZIDINE T. HAUET, H. BAUMERT, I. BEN AMOR, H. GIBELIN, C. TALLINEAU, M. EUGENE, J-P. TILLEMENT and M. CARRETIER J. Pharmacol. Exp. Ther., 2000, 292(1), 254-260.

2 In Vitro BINDING AND PARTITIONING OF IRINOTECAN (CPT-11) AND ITS METABOLITE, SN-38, IN HUMAN BLOOD. Olivier COMBES, Jér™me BARRÉ, Jean-Claude DUCHÉ, Laurent VERNILLET, Yves ARCHIMBAUD, Michael P. MARIETTA, Jean-Pal TILLEMENT and Saïk URIEN Investigational New Drugs, 2000, 18, 1-5.

3 EVIDENCE FOR DIFFERENT INTERACTIONS BETWEEN ß1- AND ß2- ADRENOCEPTOR SUBTYPES WITH ADENYLYL CYCLASE IN THE RAT BRAIN : A CONCENTRATION-RESPONSE STUDY USING FORSKOLIN D. MORIN, R. SAPENA, J-P. TILLEMENT and S. URIEN Pharmacol. Res., 2000, 41(4), 435-443.

4 [3H]-TRIMETAZIDINE MITOCHONDRIAL BINDING SITES : REGULATION BY CATIONS, EFFECT OF TRIMETAZIDINE DERIVATIVES AND OTHER AGENTS AND INTERACTION WITH AN ENDOGENOUS SUBSTANCE D. MORIN, R. SAPENA, A. ELIMADI, B. TESTA, S. LABIDALLE, A. LE RIDANT & J-P. TILLEMENT Brit J Pharmacol, 2000, 130, 655-663.

5 EXPRESSION OF THE GENETIC VARIANTS OF HUMAN ALPHA-1-ACID GLYCOPROTEIN IN CANCER J-C. DUCHÉ, S. URIEN, N. SIMON, E. MALAURIE, I. MONNET and J. BARRÉ Clinl Biochem, 2000, 33(3), 197-202.

6 S-15176 REDUCES THE HEPATIC INJURY IN RATS SUBJECTED TO EXPERIMENTAL ISCHEMIA AND REPERFUSIONN A. SETTAF, M. ZAHIDY, A. ELIMADI, R. SAPENA, I.ABD ALSAMAD, J-P. TILLEMENT and D. MORIN Eur. J. Pharmacol., 2000, 406, 281-292.

7 LOW GLUCOCORTICOID CONCENTRATIONS DECREASE OXIDATIVE PHOSPHORYLATION OF ISOLATED RAT BRAIN MITOCHONDRIA : AN ADDITIONAL EFFECT OF DEXAMETHASONE C. MORIN. R. ZINI, N. SIMON, P. CHARBONNIER, J-P TILLEMENT and H. LE LOUET Fundam. Clin. Pharmacol., 2000, 14, 493-500.

8 THE SIGNIFICANCE OF PLASMA-PROTEIN BINDING IN DRUG RESEARCH S. URIEN, J-P. TILLEMENT and J. BARRÉ In PHARMACOKINETIC OPTIMIZATION IN DRUG RESEARCH. Biological, physicochemical and computational strategies. B. TESTA, H. VAN DE WATERBEEMD, G. FOLKERS, R. GUY. Helvetica Chimica Acta, 2000, 189-197.

9 NEW INSIGHTS INTO THE SECOND GENERATION ANTIHISTAMINES G.M.WALSH, L.ANNUNZIATO, N. FROSSARD, K.KNOL, S.LEVANDER, J-M.NICOLAS, M.TAGLIALATELA, M.D.THARP, J-P.TILLEMENT AND H.TIMMERMAN. Drugs, 2001, 61(2), 207-236.

2001

1 S15176 AND S16950 INTERATION WITH CYCLOSPORIN A ANTIPROLIFERATIVE EFFECT ON CULTURED HUMAN LYMPHOCYTES E.ALBENGRES, J-P. TILLEMENT, H. LE LOUET, P. D'ATHIS Fundamental & Clinical Pharmacology, 2001, 15, 41-46.

2 MITOCHONDRIA AS TARGET FOR ANTIISCHEMIC DRUGS D.MORIN, T.HAUET, M.SPEDDING, J-P. TILLEMENT Advanced drug delivery reviews, 2001, 49, 151-174.

3 CURCUMIN INDUCES THE MITOCHONDRIAL PERMEABILITY TRANSITION PORE MEDIATED BY MEMBRANE PROTEIN THIOL OXIDATION D.MORIN, S.BARTHELEMY, R.ZINI, S.LABIDALLE, J-P. TILLEMENT FEBS Letters, 2001, 495, 131-136.

4 STRUCTURAL DAMAGE TO PROTEINS CAUSED BY FREE RADICALS : ASSESSMENT, PROTECTION BY ANTIOXIDANTS, AND INFLUENCE OF PROTEIN BINDING A.SALVI, P-A.CARRUPT, J-P.TILLEMENT, B.TESTA Biochemical Pharmacology, 61, 2001, 1237-1242.

5 EFFECT OF ANTIDEPRESSANTS ON EXTRACELLULAR CATECHOLAMINE CONCENTRATIONS IN THE RAT HIPPOCAMPUS USING IN VIVO MICRODIALYSIS R.ZINI, J-P.TILLEMENT, D.MORIN Biologie & Santé, 1, 2000, 6-13.

BOOKS (editor and translator)

1 SAVOIR PRESCRIRE : I – PATHOLOGIE CARDIOVASCULAIRE II – PATHOLOGIE PULMONAIRE ET DIGESTIVE III – PATHOLOGIE ENDOCRINIENNE IV – PATHOLOGIE NEUROLOGIQUE ET PSYCHIATRIQUE V – PATHOLOGIE RHUMATOLOGIQUE J-P.TILLEMENT et Collaborateurs La couleuvre d'Esculape, 1978, 1979, 1980 et 1981

2 PHARMACOLOGIE CLINIQUE – BASES DE LA THERAPEUTIQUE J-P.GIROUD, G.MATHE, G.MEYNIEL Expansion Scientifique Française, 1988 Pharmacologie Générale ; coordinateurs J-P.TILLEMENT and J.KOCH-WESER

3 ALPHA1 – ACID GLYCOPROTEIN : GENETICS, BIOCHEMISTRY, PHYSIOLOGICAL FUNCTIONS AND PHARMACOLOGY Progress in Clinical and Biological Research, Volume 300, 1989 P.BAUMANN, C.B.EAP, W.E.MULLER and J.P.TILLEMENT Alan R.Liss, Inc, New York.

4 PLASMA BINDING OF DRUGS AND ITS CONSEQUENCES R.BELPAIRE, M.BOGAERT, J.P.TILLEMENT, R.VERBEECK Academia press, Ghent, 1991.

5 BLOOD BINDING OF DRUGS J.P.TILLEMENT, R.ZINI and J.BARRÉ Encyclopedia of Human Biology, edited by R.DULBECCO, Academic Press and Harcourt Brace Javanovich, New York, 1991, 607-613.

6 HUMAN PHARMACOLOGY THE BASIS OF CLINICAL PHARMACOLOGY H.KUEMMERLE, T.SCHIBUYA and J.P.TILLEMENT Elsevier, Amsterdam, London, New York, Tokyo, 1991.

7 BLOOD BINDING AND DRUG TRANSFER J.P.TILLEMENT and H.ECKERT Fort et Clair, Paris, 1993.

8 LES BASES PHARMACOLOGIQUES DE L'UTILISATION DES MEDICAMENTS J.P.TILLEMENT, P.ALLAIN, G.HOUIN, B.VANDEL Edition française de « THE PHARMACOLOGICAL BASIS OF THERAPEUTICS » Goodman et Gilman, edited by Mc GRAW-HILL, Berkshire, 1998 (French Version) Goodman et Gilman, edited by Mc GRAW-HILL, New York, 1996 (American Version)

9 EUROPEAN TEXTBOOK OF CLINICAL PHARMACOLOGY edited by C.SIRTORI, coeditors J.KUHLMANN, J.P.TILLEMENT, B.VRHOVAC Clinical Medicine Series, Mc GRAW-HILL, Berkshire, 2000.

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