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Expert DMPK Consulting for Streamlined Drug Discovery and Development.

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ADMEDDICON – DMPK Consulting is an independent preclinical consulting firm supporting biotech start-ups, university spin-offs and venture capitalists in bringing their assets from discovery into clinical stage development.

Partnering with you to overcome the challenges of drug development

Drug discovery without considering monetary constraints is already a challenge. When funding is limited, the definition of key questions, smart experimental design, and, if relevant, consideration of regulatory frameworks become critical aspects in achieving the next project milestone in a scientifically sound and cost-efficient manner.

During the past 25 years in Swiss pharma and biotech companies, I have helped bringing more than 50 drug candidates from lead discovery to clinical stage development, eight of which finally received marketing authorization and improve patients´ quality of life. ADMEDDICON thus has the expertise to support your projects with its proven scientific excellence, cost consciousness and regulatory experience.

The range of ADMEDDICON services covers all aspects of pharmacokinetic optimization and characterization, ranging from early lead profiling to candidate selection, PK/PD correlations, formulation strategies for pharmacology and toxicology programs, first-in-human packages including toxicokinetics, drug-drug interaction strategies from in vitro data to clinical trials, metabolite safety assessments, and scientific consultancy for human ADME studies.

For questions outside its core competence, ADMEDDICON works with a network of qualified experts in the field of toxicology, regulatory, CMC, research informatics and early clinical development.

I am a strong believer in interdisciplinary science and a lover of jazz music. Discovering drugs in fact has a lot in common with making music. It needs talented individuals that master their own instruments, but all equally need to listen to the sound of their neighbors.

Services

Strategic Consulting

  • DMPK strategies for lead optimization
  • DMPK strategies for and beyond IND-enabling programs
  • Drug-drug interaction strategies (from test tube to clinical trial)
  • Strategic positioning for in- and outlicensing opportunities

Scientific Consulting

  • Design of lead optimization programs
  • DMPK trouble-shooting
  • PK/PD analyses
  • Bioanalytics
  • Formulation strategies for pharmacology and toxicology
  • Toxicokinetics
  • Human ADME studies

Operational Consulting

  • DMPK project management
  • CRO selection
  • External study monitoring
  • Interim management

Regulatory Writing

  • Investigator´s Brochures
  • Investigational New Drug Applications
  • Scientific Advice Briefing Books
  • Regulatory Filings (US FDA, EMA, PMDA)

Profile

I am an organic chemist by education but gradually moved away from synthetic chemistry during my PhD thesis looking into mechanisms of natural DNA damage and thus the molecular origin of evolution. As a postdoc, I worked on the metabolic activation of thiophene-containing drugs and their toxicity to the liver. This work opened the door to pharmaceutical industry which had just recognized the value of integrating pharmacokinetic and toxicological optimization early into the drug discovery process.

After four years at F. Hoffmann-La Roche AG in Basel as a drug metabolism scientist, I joined the newly created Actelion Pharmaceuticals Ltd to build a DMPK organization covering the entire process from lead optimization up to regulatory filing. In 2017, Actelion was acquired by Johnson & Johnson for 30 billion USD, and the research and early development units were transferred into a new company, Idorsia Pharmaceuticals Ltd. I was part of its research management team and thus co-responsible for the strategic, scientific and organizational management of a 35-project pipeline.


Early in 2024, I founded ADMEDDICON – DMPK Consulting, an independent preclinical consulting firm with the idea to share my strategic and scientific experience in collaborations with biotech companies, university spin-offs and venture capital firms.

1996-2000

Laboratory Head, Preclinical Drug Metabolism, F. Hoffmann – La Roche AG, Basel

2000-2004
Director, Head Nonclinical DMPK, Actelion Pharmaceuticals Ltd, Allschwil

2004-2009

Senior Director, Head Nonclinical DMPK, Actelion Pharmaceuticals Ltd

2009-2017

Vice President, Head Nonclinical DMPK, Actelion Pharmaceuticals Ltd
2017-2023
Vice President, Head Nonclinical DMPK, Idorsia Pharmaceuticals Ltd, Allschwil
2011-2023
Deputy Head Nonclinical Development, Actelion and Idorsia Pharmaceuticals Ltd
2024
Founder and Managing Director ADMEDDICON – DMPK Consulting

1984-1990

Chemistry studies at the universities of Heidelberg (Germany) and Bristol (UK). Diploma thesis on rearrangement reactions of substituted triarylamines; awarded with a grant of the Dr. Sophie-von-Bernthsen fond. Fellow of Studienstiftung des Deutschen Volkes and Deutscher Akademischer Austauschdienst.

1991-1994

University of Würzburg, Germany, PhD thesis on mechanisms of DNA damage by natural peroxides.

1995-1996

Centre National de la Recherche Scientifique, Paris, France, Postdoctoral stage on drug-induced liver toxicity of thiophene-containing drugs. Fellow of the Deutsche Forschungsgemeinschaft.
  1. Treiber, S. Seeland, B. Hashimi, J. Williams, H. Aissauoi. The metabolism of the selective orexin 1 receptor antagonist nivasorexant. Xenobiotica, 2024, 54, 124-137. (Download PDF)
  1. Treiber, S. Seeland, J. Segrestaa, C. Lescop, M. H. Bolli. Reversible oxidation/reduction steps in the metabolic degradation of the glycerol side chain of the S1P1 agonist ponesimod. Xenobiotica, 2024, 54, 182-194. (Download PDF)
  1. A. Steiner, L. Botticelli, G. Bergamini, E. Micioni di Bonaventura, J. Gatfield, J. Williams, A. Treiber, C. Vaillant, C. Cifani, M. V. Micioni di Bonaventura. Evaluation of the selective orexin receptor antagonist nivasorexant in an animal model of binge eating disorder, J Eat Disorders, 2024, doi: 10.1002/eat.24181. PMID: 38456603.
  1. T. Williams, M. H. Bolli, C. Brotschi, C. Roch, T. Sifferlen, M. A. Steiner, A. Treiber, J. Gatfield, C. Boss. Discovery of nivasorexant (ACT-539313): The first selective orexin-1-receptor antagonist (SO1RA) investigated in clinical trials. J. Med. Chem., 2024, 67, 344-354.
  1. Brotschi, M. H. Bolli, J. Gatfield, C. Roch, T. Sifferlen, A. Treiber, J. T. Williams, C. Boss. Pyrazole derivatives as selective orexin-2 antagonists (2-SORA): synthesis, structure-activity relationship, and sleep-promoting properties in rats. Royal Soc. Chem. Med Chem. J., 2024, 15, 334-354.
  1. Berger, P. Kaufmann, M. Berse, A. Treiber, N. Grignaschi, J. Dingemanse. Effect of nivasorexant (ACT‑539313), a selective orexin-1 receptor antagonist, on multiple cytochrome P450 probe substrates in vitro and in vivo using a cocktail approach in healthy subjects. Pharmacol. Res. Perspect., 2023, 11:201143, DOI:10.1002/prp2.1143.
  1. Treiber, H. Aissaoui, S. Delahaye, S. Glutz, J. Grimont, C. Müller, S. Seeland, V. Siefken, C. Boss. CYP3A4 catalyzes the rearrangement of the dual orexin receptor antagonist daridorexant to 4-hydroxy piperidinol metabolites. Chem. Med. Chem., 2023, 18, e202300030, DOI:10.1002/cmdc.202300030. (Download PDF)
  1. Treiber, S. Delahaye A. Weigel, P. Aeänismaa, J. Gatfield, S. Seeland. The metabolism of the dual orexin receptor antagonist daridorexant. Xenobiotica, 2023, 53, 173-183.
  1. Treiber and M. H. Bolli. The bile salt export pump BSEP, in The Medicinal Chemist’s Guide to Solving ADMET Challenges (ed. P. Schnider), Royal Society of Chemistry, 2021, chapter 8, 160-171.
  1. Boss, J. Gatfield, C. Brotschi, B. Heidmann, T. Sifferlen, M. von Raumer, G. Schmidt, J.T. Williams, A. Treiber, C. Roch. The quest for the best dual orexin receptor antagonist (daridorexant) for the treatment of insomnia disorders. Chem. Med. Chem., 2020, 15, 2286-2305.
  1. Treiber, S. Delahaye, S. Seeland, C. Gnerre. The endothelin receptor antagonist macitentan for the treatment of pulmonary arterial hypertension: a cross-species comparison of its cytochrome P450 induction pattern. Pharmacol. Res. Perspect, 2020, 00:e00619; https://doi.org/ 10.1002/prp2.619. (Download PDF)
  1. Brotschi, M.H. Bolli, J. Gatfield, B. Heidmann, F. Jenck, C. Roch, T. Sifferlen, A. Treiber, J. T. Williams, C. Boss. From oxadiazole to triazole analogues: optimization towards a dual orexin receptor antagonist with improved in vivo efficacy in dogs. Chem. Med. Chem, 2020, 15, 1-20.
  1. Brotschi, C. Roch, J. Gatfield, A. Treiber, J. T. Williams, T. Sifferlen, B. Heidmann, F. Jenck, M.H. Bolli, C. Boss. Oxadiazole derivatives as dual orexin receptor antagonists: synthesis, structure-activity relationship, and sleep-promoting properties in rat. Chem. Med. Chem, 2019, 14, 1257-1270.
  1. Ichikawa, T. Yamada, A. Treiber, C. Gnerre, J. Segrestaa, S. Seeland, K. Nonaka. Cross-species comparison of the metabolism and excretion of selexipag. Xenobiotica, 2019, 49, 284-301.
  1. Ichikawa, T. Yamada, K. Nonaka, A. Treiber, C. Gnerre, K. Seya, S. Ochi. Pharmacokinetics of the selective prostacyclin receptor agonist selexipag in rats, dogs, and monkeys. Xenobiotica, 2018, 48, 186-196.
  1. Gnerre, J. Segrestaa, S. Seeland, P. Aeänismaa, T. Pfeifer, S. Delahaye, R. de Kanter, T. Ichikawa, T. Yamada, A. Treiber. The metabolism and drug-drug interaction potential of the selective prostacyclin receptor agonist selexipag. Xenobiotica, 2017, Aug 30, 1-16.
  1. Treiber, R. de Kanter, C. Roch, J. Gatfield, C. Boss, M. von Raumer, B. Schindelholz, C. Mühlan, J. van Gerven, F. Jenck. The use of PBPK modeling in the discovery of the dual orexin antagonist ACT-541468. J. Pharmacol. Exp. Ther., 2017, 362,489-503. (Download PDF)
  1. H. Bolli, C. Boss, A. Treiber, J. Gatfield. The discovery of macitentan – A standard medicinal discovery program? In: S. Chackalamannil, D. P. Rotella and S. E. Ward (eds.). Comprehensive Medicinal Chemistry III, 2017, vol. 8, 252-283.
  1. Heidmann, J. Gatfield, C. Roch, A. Treiber, S. Tortoioli, C. Brotschi, J. T. Williams, M. H. Bolli, T. Sifferlen, F. Jenck, C. Boss. Discovery of highly potent dual orexin receptor antagonists via a scaffold hopping approach. Chem. Med. Chem, 2016, 11, 2132-2146.
  1. de Kanter, P. Sidharta, S. Delahaye, C. Gnerre, J. Segrestaa, S. Buchmann, C. Kohl, A. Treiber. Physiologically-based pharmacokinetic (PBPK) modeling of macitentan: prediction of drug-drug interactions. Clin. Pharmacokin., 2016, 55, 369-380.
  1. Caroff, F. Hubler, E. Meyer, D. Renneberg, A. Treiber, M. Rey, P. Hess, B. Steiner, K. Hilpert, M. A. Riederer. 4-((R)-2-{[6-((S)-3-Methoxy-pyrrolidin-1-yl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester (ACT‑246475), a novel P2Y12 receptor antagonist with an improved in vivo efficacy/safety ratio. J. Med. Chem., 2015, 58, 9133-9153.
  1. Treiber, T. Miraval, M. H. Bolli, J.-A. Funel, J. Segrestaa, S. Seeland. The metabolism of the dual endothelin receptor antagonist macitentan in the rat and dog. Xenobiotica., 2015, 4, 1-15.
  1. T. Williams, J. Gatfield, C. Roch, A. Treiber, F. Jenck, M. H. Bolli, T. Sifferlen, B. Heidmann, C. Boss. Discovery and optimization of 2-benzyl pyrrolidine carboxamides as potent dual orexin antagonists. Chem Med Comm, 2015, 6, 1054-1064.
  1. Sifferlen, A. Boller, A. Chardonneau, E. Cottreel, J. Gatfield, A. Treiber, C. Roch, F. Jenck, H. Aissaoui, J. T. Williams, C. Brotschi, B. Heidmann, R. Siegrist and C. Boss. Substituted pyrrolidin-2ones: Centrally acting orexin receptor antagonist promoting sleep. Bioorg. Med. Chem. Lett., 2015, 25, 1884-1891.
  1. N. Sidharta, A. Treiber, J. Dingemanse. Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan: A systematic review. Clin. Pharmacokin. 2015, 54, 457-471.
  1. Seeland, H. Kettiger, M. Murphy, A. Treiber, J. Giller, A. Kiss, R. Sube, S. Krähenbühl, M. Hafner, J. Huwyler. ATP-induced cellular stress and mitochondrial toxicity in cells expressing purinergic P2X7 receptor. Pharmacol. Res. Perspectives, 2015, 3, e00123.
  1. Gehin, P. N. Sidharta, C. Gnerre, A. Treiber, A. Halabi, J. Dingemanse. Pharmacokinetic interactions between simvastatin and setipiprant, a CRTH2 antagonist. Eur. J. Clin. Pharmacol., 2015, 71. 15-23.
  1. Boss, C. Roch-Brisbare, A. Treiber, M. A. Steiner, F. Jenck, M. von Raumer, T. Sifferlen, C. Brotschi, M. Bolli, B. Heidmann, J. Williams, H. Aissaoui, R. Siegrist and J. Gatfield. Structure-activity relationship, biological and pharmacological characterization of the proline sulfonamide ACT-462206, a highly potent, brain-penetrant dual orexin 1/ orexin 2 receptor antagonist. Chem Med Chem, 2014, 9. 2486-2496.
  1. Caroff, E. Meyer, A. Treiber, K. Hilpert, M. Riederer. Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable, and selective P2Y12 antagonists for inhibition of platelet aggregation. Bioorganic & Medicinal Chemistry Letters 2014, 24, 4323-4331.
  1. Treiber, P. Aänismaa, R. de Kanter, S. Delahaye, M. Treher, P. Hess, P. Sidharta. Macitentan does not interfere with hepatic bile salt transport. J. Pharm. Exp. Ther. 2014, 350, 130-143. (Download PDF)
  1. Sifferlen, A. Boller, A. Chardonneau, E. Cottreel, J. Höcker, H. Aissoui, J. T. Williams, B. Heidmann, R. Siegrist, T. Weller, J. Gatfield, A. Treiber, C. Brisbare-Roch, F. Jenck, C. Boss. Discovery of substituted lactams as novel, dual orexin receptor antagonists. Synthesis, preliminary structure activity relationship studies and efforts towards improved metabolic stability and pharmacokinetic properties. Part I. Bioorg. Med. Chem. Lett., 2014, 24, 1201-1208.
  1. H. Bolli, C. Müller, B. Mathys, S. Abele, M. Birker, R. Bravo, D. Bur, C. Kohl, D. Lehmann, O. Nayler, M. Rey, S. Meyer, M. Scherz, G. Schmidt, B. Steiner, A. Treiber, J. Velker, T. Weller. Novel S1P1 receptor agonists – Part 1: From pyrazoles to thiophenes. J. Med. Chem.2013, 56, 9737-9755.
  1. A. Steiner, J. Gatfield, C. Brisbare-Roch, H. Dietrich, F. Jenck, A. Treiber, F. Jenck, C. Boss. Discovery and characterization of ACT-335827, an orally available, brain-penetrant orexin receptor type-1 selective antagonist. J. Med. Chem., 2013, 8, 898-903.
  1. Seeland, M. Török, H. Kettiger, A. Treiber, M. Hafner, J. Huwyler. A cell-based, multi-parametric sensor approach characterises drug-induced cytotoxicity in human liver HepG2 cells. Toxicology in vitro 2013, 27, 1109-1120.
  1. Dingemanse, A. Treiber, K. Shakeri-Nejad, G. Hopfgartner, P. Hoever. Elucidation of the metabolic pathways and the resulting multiple metabolites of almorexant, a dual orexin receptor antagonist, in humans. Drug Metab. Dispos. 2013, 41, 1046-1059.
  1. Fahrmayr, J. König, D. Auge, M. Mieth, J. Segrestaa, T. Pfeifer, A. Treiber, M. F. Fromm. Phase I and II metabolism and MRP2-mediated export of bosentan in a MDCKII-OATP1B1-CYP3A4-UGT1A1-MRP2 quadruple-transfected cell line. Br. J. Pharmacol. 2013, 169, 21-33.
  1. H. Bolli, C. Boss, C. Binkert, S. Buchmann. D. Bur, P. Hess, M. Iglarz, S. Meyer, J. Rein, M. Rey, A. Treiber, M. Clozel, W. Fischli, T. Weller. The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N’-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist. J. Med. Chem. 2012, 55, 7849-7861.
  1. Bruderer, G. Hopfgartner, M. Seiberling, J. Wank, A. Treiber, J. Dingemanse. Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans. Xenobiotica, 2012, 14, 901-910.
  1. Bruderer, P. Aeänismaa, M.C. Homery, S. Häusler, K. Landskroner, P. Sidharta, A. Treiber, J. Dingemanse. Effect of cyclosporine A and rifampicin on the pharmacokinetics of macitentan, a tissue-targeting endothelin receptor antagonist. AAPS J. 2012, 68-78.
  1. Seeland, A. Treiber, M. Hafner, J. Huwyler. On-line identification of P-glycoprotein substrates by monitoring of extracellular acidification and respiration rates in living cells. Biochim. Biophys. Acta – Biomembranes 2011, 1808, 1827-1831.
  1. Landskroner, P. Hess, A. Treiber. Surgical and pharmacological animal models used in drug metabolism and pharmacokinetics, Xenobiotica 2011, 48, 687-700.
  1. Corminboeuf, O. Bezencon, L. Remen, C. Grisostomi, S. Richard-Bildstein, D. Bur, L Prade, P. Strickner, P. Hess, W. Fischli, B. Steiner, A. Treiber. Piperidine-based renin inhibitors: upper chain optimization. Bioorg. Med. Chem. Lett. 2010, 20, 6291-6296.
  1. Corminboeuf, O. Bezencon, C. Grisostomi, L. Remen, S. Richard-Bildstein, D. Bur, L Prade, P. Hess, P. Strickner, W. Fischli, B. Steiner, A. Treiber. Design and optimization of new piperidines as renin inhibitors. Bioorg. Med. Chem. Lett. 2010, 20, 6286-6290.
  1. H. Bolli, S. Abele, C. Binkert, R. Bravo, S. Buchmann, D. Bur, J. Gatfield, P. Hess, C. Kohl, C. Mangold, B. Mathys, K. Menyhart, C. Müller, O. Nayler, M. Scherz, G. Schmidt, V. Sippel, B. Steiner, D. Strasser, A. Treiber, T. Weller. 2-Imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists. J. Med. Chem. 2010, 53, 4198–4211
  1. Remen, O. Bezençon, S. Richard-Bildstein, D. Bur, L. Prade, O. Corminboeuf, C. Boss, C. Grisostomi, T. Sifferlen, P. Strickner, P. Hess, S. Delahaye, A. Treiber, T. Weller, C. Binkert, B. Steiner, W. Fischli. New classes of potent and bioavailable human renin inhibitors. Bioorg. Med. Chem. Lett., 2009, 19, 6762-6765.
  1. Bezençon, D. Bur, T. Weller, S. Richard-Bildstein, L. Remen, T. Sifferlen, O. Corminboeuf, C. Grisostomi, L. Prade, S. Delahaye, A. Treiber, P. Strickner, P. Hess, B. Steiner, and W. Fischli. Design and preparation of potent, non-peptidic, bioavailable renin inhibitors. J. Med. Chem., 2009, 52, 3689-3702.
  1. L.M. van Giersbergen, A. Treiber, J. Dingemanse. In vitro and in vivo pharmacokinetic characteristics of clazosentan, an intravenous endothelin receptor antagonist, in humans, Int. J. Clin. Pharm. Ther. 2009, 47, 169-177.
  1. Aissaoui, R. Koberstein, C. Zumbrunn, J. Gatfield, C. Brisbare-Roch, F. Jenck, A. Treiber, C. Boss. N-Glycine-sulfonamides as potent dual orexin-1/orexin-2 receptor antagonists. Bioorg. Me.l Chem. Lett. 2008, 18, 5729-5733.
  1. Iglarz, C. Binkert, K. Morrison, W. Fischli, J. Gatfield, A. Treiber, T. Weller, M.H. Bolli, C. Boss, S. Buchmann, B. Capeleto, P. Hess, C. Qiu, M. Clozel. Pharmacology of macitentan, an orally active, tissue-targeting dual endothelin receptor antagonist. J. Pharm. Exp. Ther. 2008, 327, 736-745.
  1. Treiber, O. Morand, M. Clozel. The pharmacokinetics and tissue distribution of miglustat in the rat, Xenobiotica 2007, 37, 298-314.
  1. Treiber, R. Schneiter, S. Häussler, B. Stieger. Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin and sildenafil, Drug Metab. Dispos. 2007, 35, 1400-1408. (Download PDF)
  1. L.M. van Giersbergen, A. Treiber, R. Schneiter, H. Dietrich, J. Dingemanse. Inhibitory and inductive effects of rifampicin on the pharmacokinetics of bosentan in healthy subjects, Clin. Pharm. Ther. 2007, 81, 414-419.
  1. H. Bolli, J. Marfurth, C. Grisostomi, C. Boss, C. Binkert, P. Hess, A. Treiber, E. Thorin, K. Morrison, S. Buchmann, D. Bur, H. Ramuz, M. Clozel, W. Fischli, T. Weller. Novel benzo-(1,4)-diazepin-2-one derivatives as endothelin receptor antagonists. J. Med. Chem. 2004, 47, 2776-2795
  1. Treiber, R. Schneiter, S. Delahaye, M. Clozel. Inhibition of organic anion transporting polypeptide-mediated hepatic uptake is the major determinant in the pharmacokinetic interaction between bosentan and cyclosporin A in the rat. J. Pharm. Exp. Ther. 2004, 308, 1121-1129.
  1. Koberstein, H. Aissaoui, D. Bur, M. Clozel, W. Fischli, F. Jenck, C. Müller, O. Nayler, T. Sifferlen, A. Treiber, T. Weller. Tetrahydroisoquinolines as orexin receptor antagonists: strategies for lead optimization by solution-phase chemistry. Chimia 2003, 57, 270-275.
  1. Treiber, P.L.M. van Giersbergen, J. Dingemanse. In vivo and in vitro disposition profile of tezosentan, an intravenous dual endothelin receptor antagonist, in humans. Xenobiotica 2003, 33, 399-414.
  1. Rasmussen, P.H. Poulsen, A. Treiber, S. Delahaye, A. Tankisi, G.E. Cold, K. Therkelsen, A. Gjedde, J. Astrup. No influence of the endothelin receptor antagonist bosentan on basal and indomethacin-induced reduction of cerebral blood flow in pigs. Acta Anaesthesiol. Scand., 2003, 47 (2), 200-207.
  1. L.M. van Giersbergen, C. Gnerre, A. Treiber, J. Dingemanse, U.A. Meyer. Bosentan, a dual endothelin receptor antagonist, activates the pregnane X nuclear receptor. Eur. J. Pharmacol. 2002, 450 (2), 115-121.
  1. Treiber, P.M. Dansette, D. Mansuy. Mechanism of the aromatic hydroxylation of thiophene by acid-catalyzed peracid oxidation. J. Org. Chem. 2002, 67, 7261-7266.
  1. L.M. van Giersbergen, A. Treiber, M. Clozel, F. Bodin, J. Dingemanse. In vitro and in vivo studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide. Clin. Pharmacol. Ther. 2002, 71, 253-262.
  1. P. Märki, …, A. Treiber, … Piperidine renin inhibitors: from leads to drug candidates. Farmaco 2001, 56, 21-27.
  1. T. Ho, A. Treiber, D. Mansuy, P.M. Dansette. Oxidation of 2-(4-chlorobenzoyl)-thiophene into 1-oxide Diels-Alder dimers, sesquioxide and a sulfone-water adduct. Tetrahedron Letters 1998, 39, 5049-5052.
  1. Treiber, P.M. Dansette, H. El Hamri, D. Ginderow, J. P. Mornon, D. Mansuy. Preparation and complete characterization of thiophene-S-oxide dimers from chemical and biological oxidation of thiophene: evidence for intermediate formation of thiophene-S-oxide in thiophene metabolism in vivo and in vitro. J. Am. Chem. Soc. 1997, 119, 1565-1571.
  1. Adam, R. Stössel, A. Treiber. The SN2-reactivity of 3,3-disubstituted 1,2-dioxetanes with morpholine. J. Org. Chem. 1995, 60, 2879-2884.
  1. Adam, A. Treiber. Oxidation of acetylated guanosine by 3,3-disubstituted 1,2-dioxetanes through nucleophilic attack on the peroxide bond: model studies on the oxidative DNA damage by reactive peroxides. J. Am. Chem. Soc. 1995, 117, 2686-2693.
  1. Adam, L. Hadjiarapoglou, K. Mielke, A. Treiber. Competitive epoxidation and quinone formation in the dimethyldioxirane oxidation of diazoquinones as ambident nucleophiles. Tetrahedron Letters 1994, 35, 5625-5628.
  1. Adam, H. M. Harrer, A. Treiber. Synthesis of 1,4-dioxa-2l5-phosphorinanes by insertion of triphenylalkylidene phosphoranes into the peroxide bond of 1,2-dioxetanes: thermolysis, hydrolysis and Wittig olefination. J. Am. Chem. Soc. 1994, 116, 7581-7587.
  1. Adam, A. Treiber. 1,3-Dioxolane formation by nucleophilic attack of diazoalkanes on the peroxide bond of 1,2-dioxetanes. J. Org. Chem.1994, 59, 840-844.

 

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Non-clinical safety studies for the conduct of human trials: ICH M3 (R2)

Drug-drug interactions: ICH M12

Bioanalytical method development: ICH M10

Toxicokinetics: ICH S3A

Non-clinical evaluation of anticancer drugs: ICH S9

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Safety testing of drug metabolites: MIST guideline

Human ADME studies

Human starting dose

Drug-induced liver injury

PBPK modelling

EMA

First-in-man clinical trials

PBPK modelling

Pharmacogenomics

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