Medicine and Health Sciences Commons^™

Formulation Of Buprenorphine For Sublingual Use In Neonates., Ellena A Anagnostis, Rania E Sadaka, Linda A Sailor, David E Moody, Kevin C Dysart, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVES: The only medication used sublingually in the neonate is buprenorphine for the treatment of neonatal abstinence syndrome (NAS). Compared with morphine, buprenorphine reduces the length of treatment and length of hospitalization in neonates treated for NAS. The objective of this study was to characterize the stability of ethanolic buprenorphine for sublingual administration.

METHODS: Buprenorphine solution was prepared and stored in amber glass source bottles at either 68°F to 77°F (20°C-25°C) or 36°F to 46°F (2.2°C-7.8°C). Samples were collected from each of these batches on days 0, 3, 7, 14, and 30. Additional samples were withdrawn at baseline from each …

The Incidence Of Deep Vein Thrombosis Detected By Routine Surveillance Ultrasound In Neurosurgery Patients Receiving Dual Modality Prophylaxis., Patricia C Henwood, Thomas M Kennedy, Lynda Thomson, Taki Galanis, George L Tzanis, Geno J Merli, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The optimal method of thromboprophylaxis and the value of screening ultrasonography for detection of deep venous thrombosis (DVT) in neurosurgery patients remains unclear. The goal of this study was to determine the incidence of DVT in neurosurgical patients who, by hospital protocol, receive surveillance ultrasonography of the lower extremities twice weekly, in addition to prophylaxis with unfractionated heparin and external pneumatic compression sleeves. A retrospective review of 7,298 ultrasound studies carried out on 2,593 patients over 4 years at a university neurosurgical hospital was conducted. There was a 7.4% incidence of proximal lower extremity DVT and a 9.7% total incidence …

Clinical Pharmacology As A Foundation For Translational Science., Scott A. Waldman, R J. Hohl, G L. Kearns, S J. Swan, A Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The evolution of enabling technologies and their associated perspectives into molecular mechanisms underlying disease has extended beyond the abilities of scientific and clinical structures to advance their translation into new algorithms that improve the health of patients and populations.¹ Research programs have yielded a vast array of novel molecules related to pathophysiological mechanisms that represent diagnostic and therapeutic targets which have the potential for personalized healthcare management. Yet, despite extraordinary scientific advances, routine successful translation of discovery into new therapeutic tools remains a distant vision. Beyond constraints in bridging discovery science with clinical translation due to obstacles in facilities, …

Chronic Diseases: The Emerging Pandemic., Andre Terzic, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

According to the 2011 World Health Organization Global Status Report, of the 57 million annual global deaths – a staggering 36 million or over 63% are due to chronic diseases.¹ Four noncommunicable diseases - namely cardiovascular, cancer, diabetes, and chronic respiratory diseases - emerge as the leading cause of mortality in the world, accounting respectively for 17, 7.6, 4.2, and 1.3 million deaths based on the latest available global epidemiology data. By 2020, global deaths due to chronic diseases are projected to worsen by at least 15 to 20%. It is estimated that the four major noncommunicable diseases will …

Bionic Technologies Transforming The Science Of Healthcare Delivery, Scott A. Waldman , M.D., Ph.D, Andre Terzic , M.D., Ph.D

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Individualization of patient care is creating an envisioned future in which practitioners wield a new doctor’s bag deploying individual molecular, genetic, cellular, and systems profiles. These emerging tools are refining traditional paradigms of disease palliation into nuanced patient management algorithms employing prognostic risk stratification, therapeutic response prediction, and adverse event avoidance. Advancing technologies are enabling a shift to more proximal nodes along the continuum of pathobiology. Innovations in biomarker platforms, genomic profiling, and molecular imaging reveal the earliest stages of pathophysiology, limiting systems disruption to cells and tissues while preserving integrated organ function, enabling risk mitigation and disease prevention. At …

Year In Review, Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

If examination of journal performance is a surrogate for the vitality of a discipline, the continued ascension of Clinical Pharmacology and Therapeutics (CPT) bodes well for the evolution and practice of human therapeutics in this decade. CPT has excelled as the authoritative, cross-disciplinary journal in experimental and clinical medicine devoted to publishing advances in the nature, action, efficacy and evaluation of therapeutics in humans. Building on a foundation that established the core tenets, and a framework providing the structural integrity for the field, CPT was conceived by visionary precedent editors and editorial teams who were themselves leaders of …

Revised Dose Schema Of Sublingual Buprenorphine In The Treatment Of The Neonatal Opioid Abstinence Syndrome., Walter K Kraft, Kevin Dysart, Jay S Greenspan, Eric Gibson, Karol Kaltenbach, Michelle E Ehrlich

Department of Pharmacology and Experimental Therapeutics Faculty Papers

AIMS: More than half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacological therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS.

DESIGN: Randomized, Phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine.

SETTING: Large, urban, tertiary care hospital.

PARTICIPANTS: Twenty-four term infants requiring pharmacological treatment for NAS.

MEASUREMENTS: Outcomes were neonatal safety, length of treatment and length of hospitalization.

FINDINGS: Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of …

Clinical Translational Science 2020: Disruptive Innovation Redefines The Discovery-Application Enterprise, Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Vaccines, analgesia, and antibiotics embody some of the most

enduring therapeutic breakthroughs that have transformed

medicine. Building on such fine paradigms of biomedical

innovation, the evolution of technologies has increasingly

sparked spectacular advances across the continuum of wellness

and disease-spanning medical and surgical specialties. Discovery

science—fueled by government and private sector resources—has

systematically instituted the principles of modern healthcare

delivery ensuring that medical practice is based on up-to-date

scientifi c evidence. Th e harmony between science, technology,

and resources has culminated in a golden age of discovery and

translation, eradicating infections, curing cancers, and palliating

endocrine and metabolic diseases. Indeed, …

Analysis Of The Proteome Of Human Airway Epithelial Secretions., Mehboob Ali, Erik P Lillehoj, Yongsung Park, Yoshiyuki Kyo, K Chul Kim

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Airway surface liquid, often referred to as mucus, is a thin layer of fluid covering the luminal surface that plays an important defensive role against foreign particles and chemicals entering the lungs. Airway mucus contains various macromolecules, the most abundant being mucin glycoproteins, which contribute to its defensive function. Airway epithelial cells cultured in vitro secrete mucins and nonmucin proteins from their apical surface that mimics mucus production in vivo. The current study was undertaken to identify the polypeptide constituents of human airway epithelial cell secretions to gain a better understanding of the protein composition of respiratory mucus.

RESULTS: …

The Effects Of Laropiprant, A Selective Prostaglandin D₂ Receptor 1 Antagonist, On The Antiplatelet Activity Of Clopidogrel Or Aspirin., Aimee Dallob, Wen-Lin Luo, Julie Mabalot Luk, Lisa Ratcliffe, Amy O Johnson-Levonas, Jules I Schwartz, Victor Dishy, Walter K. Kraft, Jan N De Hoon, Anne Van Hecken, Inge De Lepeleire, Waldemar Radziszewski, John A Wagner, Eseng Lai

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Laropiprant (LRPT) is being developed in combination with Merck's extended-release niacin (ERN) formulation for the treatment of dyslipidemia. LRPT, an antagonist of the prostaglandin PGD₂ receptor DP1, reduces flushing symptoms associated with ERN. LRPT also has affinity for the thromboxane A₂ receptor TP (approximately 190-fold less potent at TP compared with DP1). Aspirin and clopidogrel are two frequently used anti-clotting agents with different mechanisms of action. Since LRPT may potentially be co-administered with either one of these agents, these studies were conducted to assess the effects of steady-state LRPT on the antiplatelet activity of steady-state clopidogrel or aspirin. Bleeding time …