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Dr. Rainer K. Liedtke. M.D. has dealt with the theory and practice of medical innovations for more than 30 years. Own new concepts, findings or developments include areas of pain, stress, cell degeneration, e.g. new local pain therapies, the birth control patch, anti-depressive effects of the hormone oxytocin, new mechanisms in the action of analgesics, betablocker patches in hypertension, needle-free insulin application, new intranasal drug delivery systems, a bioinformatics development tool. That way he has reached the position of the leading expert for innovative drug technologies and "pharma design". Some of the concepts and projects are briefly outlined under Case descriptions.
Academic and Industrial Experience: Physician at hospital for several years, activities as university lecturer for pharmacology, clinical drug research, research director, CEO, company founder (i.a. EpiCept Corp). Cooperation with i.a. universities of Bonn, Erlangen, Frankfurt, Münster, Regensburg (D), Vienna and Graz (A), Zurich and Basel (CH), Edinburgh (UK), Fraunhofer Gesellschaft and Max-Planck-Institute (D). Scientific Author: Specialist books, publications and patents. Doctor's degree in medicine (University of Bonn, Institute of Physiological Chemistry): Experimental biochemical studies on DNA and RNA. Initial Research Work: Molecular medicine (i.a. by order of German Research Foundation (DFG). Current Scientific Studies: An integrated molecular model of the pain phenomenon; biochemical mechanisms of analgesics. Writer: Essays and books on topical social matters, mostly involving biological aspects (publications).
 
CASE DESCRIPTIONS OF THEORIES,
CONCEPTS AND PROJECTS
Theoretic Work on Pain and Stress Fundamentals
pain
The current conceptions to describe pain as a primarily unidirectional warning mechanism for the existence of specific damages (noxae) appear to be medically insufficient. They cannot explain the biological basic conception of this ubiquitary and profound phenomenon. A new general theory describes pain as a biophysical comprehensive and integrated mechanism (A general theory on pain as an integrated thermodynamic mechanism). It considers the occurrence of pain as a relativistic process in case of a disturbed intracellular energy cycle efficiency of an impaired cell (poster). This, in addition, makes also some actions and adverse effects of peripherally acting analgesics better explainable (A model on the induction of adverse vascular long-term effects of NSAIDs). Operatively the phenomenon of pain results from an extracellular ionic mechanism that transforms the current status of the biochemically disturbed intracellular energy status into a neuronal hyperexcitability of the terminal nerve fibers (poster). As a whole the mechanism shows the characteristics of a "pain cycle" with a reparative component. This conception as a closed loop control mechanism has been first time formulated. Another more specific theory analyses mechanisms of the clinically significant neuropathic pain, in particular the possibility of a an electrophysiological self-excitation in the case of an energetic-metabolic disturbance of the nerve cell (A special theory on the origin of neuropathic pain)
Mechanisms of NSAID Analgesics, Arteriosclerosis,
Coronary Artery Disease, Hypertension
The most frequently used analgesics today are non-steroidal anti-inflammatory drugs (NSAIDs). They are effective painkillers, but they do also cause a large number of undesirable effects in the gastrointestinal region (haemorrhage, ulcer, nausea), such as e.g. known from i.a. Aspirin (Acetylsalicylic Acid ). In addition they can damage other organs in long-term (liver, kidney, central nervous system, bone marrow).
In the context of the results of more recent clinical long-term studies, however, also these side effects appear in a different light of risk assessment. The studies showed that therapies with NSAIDs involve a significantly increased long-term cardiovascular risk and that both, so-called selective COX-2 inhibitors (i.a. Rofecoxib) and non-selective NSAIDs (i.a. Diclofenac) increase the mortality of patients with a history of myocardial infarction as well as stroke. Furthermore it is unclear in this framework whether, or to which extent, some specific NSAIDS (Naproxen, Aspirin) may be considered as having a special property of a vascular "protective" effect. That appears doubtful. Numerous scientific studies conclude, in clear contrast to such assumption, e.g. an even increased risk of stroke in context with Aspirin. Such risk appears in particular the case for people with a low cardiovascular risk.
The causes and connections of NSAIDS with cardiovascular risks are still unclear to a large extent. Based on a newly created biochemical model by means of enhanced Entity Relationship Modeling (eERM) via BMA/3.1, such long-term risks appear to be based on the induction of an imbalance in the cellular energy metabolism rather than a COX inhibition effect. This has been summarized in a further publication, which delineates an intrinsic and extrinsic (relational) mechanism of action of aspirin ("A new model on the mechanism of action of Aspirin: Ca2+ Efflux inhibitor").
The intrinsic NSAID mechanism effects a relative change of the effectivity of some ion channels , whereas the extrinsic effects depend from the different NSAID affinity to COX isomers. Consequently chemically different NSAIDs show on this secondary level different actions (accentuation of effects). A common mechanism of vascular damage appears to include all NSAID, to a certain extent.
According to that eERM model NSAID might, after a clinically still unremarkable phase, also lead to such a kind of arterial intramural calcification that can favor or trigger hypertension, infarction or stroke (Arterial Vascular Effects of Non-steroidal Antiphlogistic Drugs - A Biochemical Model on an Intramural Induction of Arteriosclerosis). In addition it should be noted, that degenerative calcifying vascular NSAID effects could also be found in experimental models. Via that eERM Modell also a cell mechanism could be derived which represents an induction of an early phase of arteriosclerosis and hypertension (Induction of an Early Hypertension by Media Calcification): A replication mechanism with an avalanche-characteristics (‘chemical self assembly’) that effects a sclerosing vascular mineralization (poster). The metastatic character of the calcifying vascular processes shows significant analogy to the frequent cardiovascular complications in chronic kidney diseases, in particular their increased mortality rates due to calcified coronary arteries (Coronary artery disease in renal dysfunction - a model of a progressive calcification by a mechanism of chemical self-assembly)
Based on these eERM model findings, at least the induction and the early phase of an arteriosclerosis and hypertension do not correlate with the lipid profiles (poster). These findings can provide a better understanding of some causes of the early phase of arteriosclerosis and hypertension and of the metastatic mechanism of the calcification. These processes are also linked with the so-called metabolic syndrome. Furthermore the findings open up new routes of therapeutic interventions for cardiovascular risks. In addition, the NSAID antiproliferative mechanism (vascular disrupting effect) also indicates possibilities for their therapeutic application in certain forms of cancer.
 
Peripheral Topical Pain Therapy
A topical (local) pain therapy opens up a treatment that involves a reduction of undesired effects, in particular in comparison with systemic applications of NSAIDS, muscle relaxants or opoids. The new concept of a topical neuronal pain therapy, using peripheral nociceptors (C- and A-delta fibers) as a target, interferes with the interactive neuronal information to the central nervous system (CNS). Sodium channel blockers (SCB) from the class of local anesthetics (LA) are acting, in their pharmacological mechanism, like a kind of peripheral "neuronal firewall" by modulating the transmission of signals to the CNS.
Based on the anatomic-functional conditions of the nociceptors, the concept for the SCB-LA then was transformed into a topical non-invasive application (skin patches). That way, these substances can be used in different doses as neural analgesics so as to produce an "analgesia without anesthesia". For this purpose until 1995 an entirely new pain patch with Lidocaine has been developed. Its delivery matrix employs lipids of natural origin having specific properties. These improve the transport of the active drug through the skin. Also a specific GMP mass production has been developed. Historically the first Pain-Patch of this kind with the local anesthetic Lidocaine entered the US market under the name LidoPain.
The practicability of the concept has been positively confirmed by clinical studies on i.a. back pain (LidoPain®BP, EpiCept) and postherpetic pain (Lidoderm®,Endo Pharmaceuticals, Versatis® Grünenthal). New studies that are based on the same development use the local anesthetic bupivacaine (Transdur®-Bupivacaine, Durect Corp).
A further product derived from this pain concept is under examination for post-operative pain. Trauma pain causes serious psychological problems. Moreover, since these patients will move very little this also often results in medical problems such as e.g. pressure sores, local ischemia, infarction, thrombosis, or infections. Injections of local anesthetics give the most satisfactory pain relief in the immediate postoperative period, however they also have a shorter duration of effect, thus must be frequently repeated and complemented by other analgesics. Therefore the general goal has been to provide patients a longer painless period (some days) after their operation, also to reduce the need of additive analgesics.
Based on these principal requirements in 1997 a new technical conception of a local „in-situ“ micro-system has been developed. In the first technical phases it has been assessed if and how such a system can fulfill the numerous biological and pharmaceutical requirements. Hereafter followed a scientific phase to further evaluate some specific aspects in local cellular pain processes. The project has now reached the phase of technical optimization for clinical application.
A project for an intensified pain therapy is the object of another development extending this concept. Within the overall cascade of the peripheral pain mechanism, it aims at a pharmacologically more comprehensive activity spectrum that also includes the inflammatory pain component. (Pharmacological Concept for a Topical Synergistic Analgesia of Peripheral Neuromuscular Pain).
Central Chemosensory Pain Therapy
Antidepressants are also used as centrally acting analgesics. But a systemic therapy with these psychopharmacological drugs mostly takes days to weeks before the therapeutic effect begins.

A concept offering an alternative to the above is based on a direct neuronal principle of operation, a "central neuroreceptor transduction". It is the objective to facilitate, by means of specifically induced neuronal signals in the Central Nervous System (CNS), a therapy that becomes active more quickly and is more selective. It makes use of the existence of pre-formed chemosensory receptors, the excitation of which allows for a direct anterograde signalling to the hypothalamic and limbic CNS. The entry function of these signals are the olfactory chemoreceptors. (Principles of topical chemosensory receptor intervention).
Based on a neurohormonally interactive model drawn up in advance. (A Neurophysiologic Model of the Circuitry of Oxytocin in Arousal, Female Distress and Depression) and as well as its predictions (i.a. via BMA/3) there was first used the peptide neuromodulator oxytocin (OXT) and studied in a validated psychopathological animal model (I. Neumann, University of Regensburg, R. Landgraf, University of Munich). A short time after its administration already, that substance produced, via the chemosensory route, distinct antidepressive and anxiolytic effects. (Intranasally applied Oxytocin: Brain uptake and effects on neuronal functions and emotionality).
Thus, the test confirmed the BMA/3 model prediction for OXT on a chemosensory route. Furthermore it substantiated pharmacological properties that had not been detected in the conventional medical application of OXT before. This needs a reconciliation of OXT's traditional pharmacological and physiological role. It is assumed that these findings will still prove to be of practical relevance to central pain therapy as well as to the therapy of depressions.
 
DEVELOPMENTS OUTSIDE PAIN THERAPIES
Transdermal Hormonal Contraception
As is already known from the transdermal hormonal substitution therapy of postmenopausal complaints, this route allows for a reduction of systemic hormonal load by means of partially bypassing the hepatic first-pass effect.
Therefore, the concept for a transdermal hormonal contraception was already drawn up by R.K. Liedtke in 1989. A respective first time and also successful practical-clinical proof then was produced in healthy young women (together with L. Wildt et al., University of Erlangen). Technically, it was realized by means of transdermal patches using the natural antagonistic sexual steroids estradiol-17ß and progesterone.
The contraceptive effects were shown my means of close-meshed measuring of numerous hormonal parameters as well as daily ultrasound measuring of the follicles. With a principally similar product the company Johnson & Johnson launched the first transdermal contraceptive on the market in the USA, years later (2002). (Evra®, www.orthoevra.com). Their clinical data confirm that contraception patches are just as effective as oral contraception ("pill").
Transdermal Beta-Blockers: Stress-induced Hypertension and Coronary Heart Disease
According to a therapeutic risk assessment (BMA/3) the usual oral dosage of beta-blockers appears to be too high for a treatment of stress-induced cardiovascular disorders. Therefore the potential of a low dosage (a "beta-blocker borderline therapy") via an alternative route was examined.
The result was, for the first time, a transdermal beta blocker therapy using Mepindolol as lead substance. The serum concentrations of that beta-blocker remained so low that blood pressure and heart rate remained unchanged to a large extent at rest, while overreactions to mental or physical stimulation were effectively controlled.
In various clinical studies, the beta-blocker patch then showed a good and lasting effectiveness in patients with arterial hypertension (together with H. Vetter, W. Vetter et al., Universities of Zurich, Münster, Bonn) and also in patients with coronary heart disease (together with J. Bonelli et al., University of Vienna). In the case of manifest attacks of angina pectoris and silent coronary ischemia, it was even more effective than transdermal nitrates. Projects of various pharmaceutical firms with other beta-blockers confirmed the effects.
Transdermal "Insulin Pump"
Insulin injection is the standard therapy for diabetes type 1 ("juvenile diabetes") but also for type 2 diabetics ("adult" diabetes) who do not sufficiently react on oral antidiabetic drugs. There is a high demand for better controlled insulin profiles of retard insulin formulations in order to improve the efficacy and safety. Alternative solutions to retard injections have already been attempted in the past with transdermal insulin patches (R. K. Liedtke, M. Sorger, F. Merk, H. Vetter, Transdermal application of insulin in type 2 diabetics: Arzneim. Forsch./Drug Res. 40(II), 884-886, (1990), and also with new oral insulin formulations (R.K. Liedtke, K. Suwelack, K. Karzel; Effect of oral and transdermal insulin preparations on the blood glucose in mice: Arzneim. Forsch./Drug Res. 40(11), 880-883, (1990). However, although with both significant effects were induced, the main therapeutic goal of an individual control in the insulin profile couldn't yet reached.
Therefore, a new project has been started. Based on a physical and mathematical model of effects of transdermal thermodynamics on skin depots (BMA/3), the new approach employs a patch that provides controlled effects by means of an "intelligent” microcontroller in order to reach a profiled release of insulin from its subcutaneous depot. This is now in an early development phase and may provide diabetics in the future more physiological profiles for injected insulin retard formulations.
 
DEVELOPMENT TOOL BMA/3.1 - A SHORT COMMENT
The new information system BMA/3.1 utilizes neuro-biological principles. It has been installed, since the current evaluation procedures, e.g. of drug properties, appear still insufficient in their projections. Presumably this is a cause that many drugs have been withdrawn from the market due a safety risk. BMA/3 employs complex models, i.a. enhanced Entity Relationship Modeling (eERM), and cybernetic processes. This approach provides an improved understanding of basic processes. Furthermore BMA/3 implements informal strategies of the human brain physiology. There exist significant differences between the routes of an analysis and assessment of a technical system and the information processes in a human brain. Therefore an algorithmic transformation of "brain strategies" is requiring a new logical approach. Consequently BMA/3 also employs a new language (FNS). Based on this BMA/3 can extract a higher number of relevant information from data pools, compared to other search systems.
 
PUBLICATIONS
books
Author of medical specialist books, scientific publications, expert reports for governmental health authorities, and more than 100 international patents, technical developments.

Books: e.g. 'Allgemeine Pharmakologie, Einführung in die Arzneimitteltherapie' (with K. Karzel, University of Bonn), 'Wörterbuch der klinischen Pharmakologie, Wörterbuch der Arzneimitteltherapie' (Editor), 'Pharmacology and Clinical Use of Angiotensin-I-Converting-Enzyme Inhibitors' (Co-editor with Franz Gross, University of Heidelberg).
Among the expert reports, an essential expert opinion referred to the first oral ACE inhibitor (Captopril). The therapy product (i.a. in the USA Capoten®) subsequently approved for the first time in a larger market was the most successful cardiovascular product worldwide for several years.
Other: Numerous medical information brochures for patients such as e.g. interactive dictionaries in the internet at Pytarg®. Publishes (i.a. in the internet) specialist articles on related areas (e.g. "General Pharmacology" ( e-script in German), "A Theoretical Model of Biological Intelligence") and as writer essays and books on topical social matters, often involving aspects of biology or information technology (e.g. "Gen Food and Health", "Genomics - the Future Risk", “Relative Intelligence” (e-book)).
Writer: Regularly issued publications on topical social matters (i.a. in the internet), mostly involving biological aspects (e.g. 'Gen Food and Health', 'Genomics - the Future Risk', 'Relative Intelligence, The relativity of intelligence as a basic principle of fitness for life' (e-book). The last book is a satirical review about evolutionary aspects of the genders ("Zum artgerechten Umgang mit Frauen"). In his time off he is amongst other things also engaged in photographing. A focus are artistic interpretations of landscapes and impressions.
 
A SELECTION OF PUBLICATIONS

R.K. Liedtke, K.O. Mosebach, An apparatus for density gradient forming and nonpuncturing fractionation, Analytical Biochemistry 62, 377 (1974) - R.K. Liedtke, I. Neukirchen, N. Lang, Nucleinsäure- und Elektrolytprofile im menschlichen Endometrium im Verlaufe des mensuellen Zyklus, Arch. Gynäkol. 220, 312 (1975) - R.K. Liedtke, Risikoverteilung beim kontrollierten Arzneimittelversuch, NJW 30, 2113 (1977) - R.K. Liedtke, Bestimmung des QRS-Winkels Alpha mittels eines mechanischen Vektorpeilers, Herz-Kreislauf 10, 202 (1978) - R. Götte, R.K. Liedtke, Zum antipyretischen Effekt von Paracetamol, Med. Klinik 73, 28 (1978) - R.K. Liedtke, W. Haase, Steady state pharmacokinetics of sulfamethoxazole and trimethoprim in man after rectal application, Arzneim. Forsch. /Drug Res. 29, 345 (1979) - S. Ebel, R.K. Liedtke, B.M.Werner, M. Richter, P. Surmann, Quantitative Bestimmung von Nitrofurantoin im Blutserum, Arch. Pharm. 321, 697 (1979), - R.K. Liedtke, B. Berner, W. Haase, W. Nicolai, R. Staab, H.H. Wagener, Vergleichende Humanpharmakokinetik von Paracetamol nach oraler und rektaler Einmalapplikation, Arzneim. Forsch./ Drug Res. 29, 1607(1979) - R.K. Liedtke, S. Ebel, E. Glaser, B. Mißler, L. Stein, Pharmakokinetische Interaktion von Paracetamol und Salicylamid nach oraler Einmaldosierung, Therapiewoche 30, 3033 (1980) - R.K. Liedtke, Clinical pharmacological aspects of the treatment of hypertension with angiotensin-converting-enzyme-inhibitors, Int. J. Clin. Pharmacol. 18, 417 (1980) - S. Ebel, R.K. Liedtke, B. Mißler, Quantitative Bestimmung von Paracetamol im Blutserum durch HPLC mit Direktinjektion, Arch. Pharm. 313, 324 (1980) - R.K. Liedtke, L. Riedl, Comparative monitoring of biochemical parameters under treatment with captopril and other antihypertensive agents, Drug Devel. Eval. 4, 107(1980) - R.K. Liedtke, S. Ebel, B. Mißler, W. Haase, L. Stein, Single dose pharmacokinetics of macrocrystalline Nitrofurantoin formulations, Arzneim. Forsch. /Drug Res. 30, 833(1980) - R.K. Liedtke, S. Ebel, B. Mißler, W. Haase, L. Stein, Humanpharmakokinetik von Paracetamol und Salicylamid nach kombinierter rektaler Mehrfachverabreichung, Arzneim. Forsch. /Drug Res. 30, 1295(1980) - S. Ebel, R.K. Liedtke, B. Mißler, Bestimmung von Salicylamid im Blut über HPLC mit Direktinjektion, Arch. Pharm. 313, 674 (1980) - R.K. Liedtke, H. Busch, H. Andersen, W. Haase, Langzeitbehandlung essentieller Hypertoniker mit dem Angiotensin-I Converting-Enzym-Hemmer Captopril und dessen Kombination mit Hydrochlorothiazid, Therapiewoche 30, 6589(1980) - R.K. Liedtke, Klinische Pharmakologie des Angiotensin-l-Converting-Enzymhemmers Captopril, Therapiewoche 31, 5258 (1981) - R.K. Liedtke, Biopharmazeutische Beeinflussung der Pharmakokinetik von Arzneistoffen in: Naber, K., Adam, D.: Chemotherapeutika im Vergleich Drug Devel. Eval. Vol. 7, 119 (1981) – R.K. Liedtke, Paracetamol; Pharmakodynamik, klinische Toxikologie und Pharmakokinetik, Med. Klinik 77, 34 (1982) - C. Spiecker, W. Vetter, St. Hany, R.K. Liedtke, H. Vetter, Transdermale Betablocker: Wirkung auf 24-Stunden-Blutdruckprofile bei Hypertoniepatienten, Schweiz. Rundsch. Med. 76, 467(1987) - C. Spiecker, W. Vetter, R.K. Liedtke, W. Zidek, H. Vetter, Transdermal Betablocker Therapy in Essential Hypertensives, American Society of Hypertention (ASH), New York 1987 - R.K. Liedtke, Pharmakodynamische Effekte des transdermal applizierten Betablockers Mepindolol bei gesunden Probanden, Schweiz. Rundsch. Med. (PRAXIS) 76 854 (1987) - C. Spieker, H. Vetter, R.K. Liedtke, W. Zidek, W. Vetter, Transdermale Betablockade bei essentieller Hypertonie, Med. Welt, 46, 1(1987) - C. Spieker, H. Vetter, R.K. Liedtke, W. Zidek, W. Vetter, Transdermal ß-blocker therapy in essential hypertension, American J. Hypertension l (1995-200S) 1988 - K. Karzel, R.K. Liedtke, Mechanismen transcutaner Resorption: Pharmakologische und biochemische Aspekte, Arzneim. Forsch. /Drug Res. 39(II), 1487(1989) - R.K. Liedtke, L. S. Chen, B. Mangold, W. Haase, Humanpharmakologische Untersuchungen zur transdermalen Anwendung von Mepindolol, Arzneim. Forsch. /Drug Res. 39(II), 1501(1989) - J. Bonelli, F. Gazo, R.K. Liedtke, Antiischämische Wirkung des transdermal applizierten ß-Rezeptorenblockers Mepindolol bei Patienten mit stabiler Angina pectoris, Arzneim. Forsch. /Drug Res. 39 (11), 1515, (1989) - J. Bonelli, F. Gazo, R.K. Liedtke, Antiischämische Wirkung des transdermal applizierten Beta-Rezeptorenblockers Mepindolol bei Patienten mit stabiler Angina pectoris. Vergleichsstudie mit transdermalem Nitrat, Arzneim. Forsch./Drug Res. 40(II), 876 (1990) - R.K. Liedtke, K. Suwelack, K. Karzel, Wirkung peroraler und transdermaler Insulin-Präparationen auf die Blutglukose bei Mäusen, Arzneim. Forsch./Drug Res. 40(11), 880 (1990) - R.K. Liedtke, M. Sorger, F. Merk, H. Vetter, Transdermale Applikation von Insulin bei Typ II Diabetikern, Ergebnisse einer klinischen Pilotstudie, Arzneim. Forsch./Drug Res. 40(II), 884 (1990) - K. Suwelack, R.K. Liedtke, K. Karzel, Untersuchungen zur Wirkung eines neuartigen transdermalen Insulin-Systems auf die Blutglukose Konzentration von Mäusen, Arch. Pharmaz. 323, 802(PD 92) (1990) - J. Bonelli, F. Gazo, P. Kirsch, R.K. Liedtke, Transdermal monotherapy with mepindolol BIO TSD in patients with stable angina pectoris, Placebo controlled cross over investigation of a new therapeutic concept with 12-hours overnight application, Int. J. Clin. Pharmacol. Toxicol 29, 425 (1991) - R.K. Liedtke, A Model for a central therapy of depressive mood and sexual distress with oxytocin, Conc. Med. Ther. (1999) - I.D. Neumann, R.K. Liedtke, M. Ludwig, R. Landgraf, Intranasally applied Oxytocin: Brain uptake and effects on neuronal functions and emotionality, Internat. Soc. PsychoNeuroEndocrinology, 31th Ann. Meetg. Melbourne (2000) - R.K. Liedtke, R. Landgraf, I.D. Neumann, Intranasally applied Oxytocin: A novel route of administration, 1st World Congress of Women's Mental Health, Berlin (2001) - R.K. Liedtke, Principles of a topical chemosensory receptor intervention; the basis for a chemosensory CNS medicine. Arzneim. Forsch./Drug Res. 52(9) 649 (2002) - R.K Liedtke, Pharmacological Concept for a topical synergistic analgesia of peripheral neuromuscular pain, Arzneim. Forsch. /Drug Res. 56(2) 108 (2006). - R.K. Liedtke, A Model on the Induction of Adverse Vascular Long-Term Effects of NSAIDs, Medicinal Chemistry, 5(1) 23 (2009) - R.K. Liedtke, A General Theory on Pain as an Integrated Thermodynamic Mechanism, Med Hypotheses (2009) 73(1):86-9, - R.K. Liedtke, Neuropathic Pain - A model of a bioenergetically controlled excitability - A new model on the mechanism of action of Aspirin: Ca2+ Efflux inhibitor PIC Res. Comm 1/2011.
Textbooks: K. Karzel, R.K. Liedtke, Allgemeine Pharmakologie, Einführung in die Grundlagen der Pharmakotherapie, G. Fischer, Stuttgart-New York, 1977 - R.K. Liedtke (Edit.) Wörterbuch der klinischen Pharmakologie für Mediziner und Pharmazeuten, G. Fischer, Stuttgart-New York, 1980 - F. Gross, R.K. Liedtke (Edits.) Pharmacology and clinical use of angiotensin-I-converting-enzyme-inhibitors, Drug Development and Evaluation Vol. 5, G. Fischer, Stuttgart-New York, 1980 - R.K. Liedtke, Allgemeine Pharmakologie in: D. Adam (Edit.) Handbuch f. Pharmareferenten, Bd.1, S.283ff, G. Fischer, Stuttgart-New York, 1980 - R.K. Liedtke (Edit.) Wörterbuch der Arzneimitteltherapie für Mediziner und Pharmazeuten, 2. erw. Aufl. G. Fischer, Stuttgart-New York, 1985 - K. Karzel, R.K. Liedtke, Einführung in die Arzneimitteltherapie, Allgemeine Pharmakologie für Mediziner und Pharmazeuten, 2. erw. Aufl. G. Fischer, Stuttgart-New York, 1985, Rainer K. Liedtke, Allgemeine Pharmakologie, Grundprinzipien der Therapie mit Arzneimitteln, E-book (2004) - Rainer K. Liedtke, Relative Intelligenz, Relativität der Intelligenz als biologisches Grundprinzip der Lebenstüchtigkeit, Internet E-book (German version 2003, 2005) - Relative Intelligence, The relativity of intelligence as a basic principle of fitness for life. E-book (english version 2006). Allgemeine Pharmakologie, Prinzipien der Wirkung von Arzneimitteln, (Kindle Edition 2011) - Lexikon Arzneimittel - Wörterbuch für Patienten (Kindle Edition 2011) - Drugs - A Translator for Patients (Kindle US Edition 2011)
 
A SELECTION OF SOME MEDICAL PATENTS
The medical, pharmaceutical and technical patents include more than hundred international applications, primarily as first application in Europe, USA, and Japan. As examples reference is made to some medical and pharmaceutical US Patents (PDF ).
 
© 2012 Rainer K. Liedtke