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Researchers
  • Prof.  Amnon Hoffman
 
Scientific Interest
The main theme of our lab is to optimize drug therapy according to pharmacokinetics and pharmacodynamics principles. This is based on both clinical and preclinical investigations, with special interests in the biological aspects of drug delivery systems. These investigations include disease state pharmacodynamics, drug-interactions as well as all the other topics listed below under research projects.
 
We have found:
Cyclosporine increases the CNS sensitivity to the action of centrally acting drugs.
The receptor-effector unit heterogeneity affects the shape of the concentration-effect profile of drugs.
Cumulative plot of the power spectrum analysis of heart rate variability enables a quantitative measurement of the autonomic nervous system activity.
 
Oral administration of GI drugs produces “first pass pharmacodynamic effect".
 
Mechanisms of intestinal lipohilic drug absorption:
  
        ·       The  degree of  intestinal  lympathic  absorption  of  lipophilic  drugs  can  be predicted  by  the uptake of  the compound to 
               chylomicrons;
 
        ·       There are parallel and unrelated absorption processes of lipophilic compounds in the enterocyte; 
 
        ·       The in-vitro lipolysis  model can be used to  predict the  optimal lipidic  vehicle, but  not when  there are significant lymphatic
               components.

  

 
Research Projects 
PK-PD rationale for optimized DDS, including GRDF.
 
Investigate the PK and PD aspects of different peptide structures including cyclization of active peptides and their optimal delivery.
 
Investigate the lymphatic absorption following intestinal or subcutaneous administrations.
 
Pharmaceutical approach to minimize microorganism resistance associated with antibiotic therapy: from preclinical studies towards clinical usage.
 
PK-PD modeling of cardiovascular drugs.
 
Mechanisms of peptide absorption.
 
 
 
Book Chapters  
Hoffman, A. Pharmacodynamic interactions between cyclosporin and CNS acting drugs. In: Progress in Clinical Pharmacy: Optimizing the Pharmacotherapy Process. Luscombe DK, Hudsson MC, and Caramona M. Eds, European Society of Clinical Pharmacy, Leiden The Netherlands, 1997, pp. 63-67.
 
Hoffman, A. Theme Issue on "Pharmacodynamic Aspects of Drug Delivery". Ed. Adv. Drug Deliv. Rev., (Preface), 1998, 33:183-184. Invited Theme Issue Editor.
 
Hoffman, A. The use of bezafibrate in the treatment of hyperlipidemia. Professional Opinion – Cardiac Risk Factors, issue 3, Bridgett Communications. 2000. Invited Review.
 
Cass, Y. and Hoffman, A. Clinical Pharmacy in Israel, In: Clinical Pharmacy in Europe, Carstensen G. Ed. European Society of Clinical Pharmacy, Leiden, The Netherlands, 2000.
 
Hoffman, A. Pharmacokinetic and pharmacodynamic aspects of gastroretentive and controlled release dosage forms. In: Optimization of oral drug delivery systems: Getting the best from your drugs. Capsugel Library, Basel, Switzerland 2002. pp.75-86.
 
Dahan, A. and Hoffman, A. Enhanced gastrointestinal absorption of lipophilic drug. In: Enhancement in Drug Delivery, Touitou, E. and Barry, B., Eds., CRC Press (Taylor & Francis Group), Boca Raton-London-New York, 2006, pp. 111-131.
 
Kadri, B. and Hoffman, A. Gastro-retentive systems. In: Encyclopedia of Pharmaceutical Technology 3rd Ed.  Swarbrick, J., Ed.Taylor & Francis Books, New York, NY, 2006.
 
Gershkovich, P., Kagan, L. and Hoffman, A. Lymphatic absorption of nanoparticles. In: Nanoparticles for Pharmaceutical Applications, Domb, A.J., Tabata, Y., Kumar, M.N.V.R., Farber, S., Eds, American Scientific Publishers, Stevenson Ranch, California, 2007, pp. 167-175.
 
 
 
Patents 
Benita, S., Donbrow, M. and Hoffman, A.: Microencapsulation by means of a cold non-solvent mixing method. Israeli Patent, 63714 (19811).
 
Donbrow, M., Benita, S. and Hoffman, A.: Production of microcapsules. Israeli Patent Application 7O431 (1984).
 
Hoffman, A., Golomb, G. and Avramoff, A.: Administration of drugs to female mammals for systemic effect. Israeli Patent application no. 101673 (1992).
 
Hoffman, A. and Afargan, M.: A pharmaceutical composition containing deprenyl. Israeli Patent application no. 107593 (1993).
 
Hoffman, A., Golomb, G. and Avramoff, A.: Compositions and devices for the intrauterine administration of drugs. International application. The Patent Cooperation Treaty (PCT) no. WO 93/20797.
 
Hoffman, A., Katzhendler, Y. and Friedman, M.: Controlled release pharmaceutical preparations, Israeli Patent application no. 115857 (1995).
 
Hoffman, A., Katzhendler, Y. and Friedman, M.: Pharmaceutical preparations for controlled release of beta-lactam antibiotics. PCT/IL97/00368 (1997).
 
Lomnicky, Y. Friedman, M. and Hoffman, A.: Controlled-release oral delivery system of drugs having presystemic biophase. Israeli Patent application no. 125780 (1998).
 
Hoffman, A., Klausner, E., Lavy, E. and Friedman, M.: Gastroretentive drug delivery system. Israeli Patent application, no. 133196 (1999).
 
Hoffman, A., Klausner, E., Lavy, E. and Friedman, M.: Gastroretentive controlled release pharmaceutical dosage form. PCT/IL00/00774 (2000).
 
Friedman, M., Klausner, E., Lavy, E. and Hoffman, A.: Gastroretentive controlled release pharmaceutical dosage forms, International Application WO0137812, (May 31, 2001).
 
Katzhendler, I.Y., Hoffman, A. and Friedman, M.: Pharmaceutical preparations for the controlled release of beta-lactam antibiotics. US 6,399,086 B1 (2002).
 
Hoffman, A., Lavy, E., Klausner, E., Friedman, M.: Gastroretentive controlled release pharmaceutical dosage forms. US Pat No 6685962 (2004).
 
Gilon, C., Hoffman, A., Linda, Y., and Hess, S.: Oral available peptidomimetic Melanocortin-4 receptor agonist PCT/IL2006/000640: WO 2006/129317 (December 7, 2006).
 
Afargan, M., Kirmayer, D., Lapidot, N., Friedman, M., Hoffman, A.: Gastro-retentive diagnostic assemblies. International Application WO 2006/072948. PCT/IL2006/000017. (January 5, 2006).
 
Hoffman, A., Gilon, C., Ovadia, O. and Linda, Y.: The Trident Motif: a novel mechanism to improve cell and membrane permeability. Israeli Patent application (2007).
 
Hoffman, A., Domb, A. and Gershkovich, P.: Orally Available apomorphine Lipophilic Prodrugs and Derivatives. US provisional patent application No 60/935,689 on (filed on 27/08/2007).
 
Breuer, E., Reich, R., Frant, J. and Hoffman, A.: Novel carbamoylphosphonates as high affinity MMP inhibitors. Israeli Patent application (2008).
 
Hoffman, A., Swed, A., and Gilon C.:  Orally available CCK-8 analog for the treatment of diabetes and metabolic diseases. Israeli Patent application (2008).
 
Hoffman, A., Swed, A., Haroutiunian, S., and Gilon C.: Orally available backbone cyclic peptide derivatives of endorphins for pain management. Israeli Patent application (2008).
 
Hoffman, A., Lavy, E., Friedman, M.: Single oral treatment of infection diseases in domestic animals by sustained release dosage form of antibiotic drugs. Israeli Patent application (2008).
 
Hoffman, A., Elgert, A., Domb, A.: Pro-nanodispersion liquid formulations for improved bioavailability and advanced biodistribution. Israeli Patent application (2008).
 
Gilon, C., Hoffman, A., Hurevich, M., Swed, A., Jubran, S., Kotler, M.: Novel macrocyclic molecules for treating or preventing HIV infection. Israeli Patent application (2008).
 
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