Respiratory diseases will induce several pathophysiological changes including gas exchange, acid-base balance, regional hemodynamics, as well as alterations of the alveolocapillary membrane. There’re a number of respiratory disease drug commercialized around the world and their pharmacological parameters are essential in medication development. Pharmacodynamics (PD) refers to the efficacy of a drug on the body and involves not the way drug receptors interact to produce responses, but quantifies drug's effects on individuals. As a service provider with high reputations, Creative Biolabs is dedicated to exploring the basic principles of PD in respiratory disorders and is capable of offering accurate pharmacology assays on that. With the help of us, clients would have a special emphasis on the pharmacodynamic considerations when treated these patients with novel drugs.
Respiratory diseases are syndromes that affect air passages, including the nasal passage, the bronchus, and the lung. They’re amongst the leading causes of death globally and represent an enormous and increasing healthcare burden across Europe. They range from acute infections (e.g. bronchitis and pneumonia) to chronic conditions (e.g. asthma and chronic obstructive pulmonary disease (COPD)). The known drugs in the market currently contain Duaklir Pressair (aclidinium bromide and formoterol fumarate), Yupelri (revefenacin), Bevespi Aerosphere (glycopyrrolate and formoterol fumarate) for COPDs, Keytruda (pembrolizumab), Tecentriq (atezolizumab), Lorbrena (lorlatinib) for non-small cell lung cancers, and so on. Respiratory disorders remain a considerable unmet medical need and it’s valid to explore whether the current approach to drug development is sophisticated enough to satisfy the needs of patients.
Some reports discussed the potency of diseases on the lung clearance of drugs, but clinically relevant data is lacking. Thus, the PD/Pharmacokinetics (PK) features of drugs in patients with asthma or COPD are being focused.
Stable asthma and COPD may not influence the disposition of theophylline or beta 2-agonists like terbutaline or salbutamol (albuterol). Important variations in theophylline PD/PK have been reported in critically ill patients, the causes of which are likely to be linked to the poor condition of patients than to a direct effect of hypoxia or hypercapnia. However, there’s a little known about the PD/PK of cromoglycate, corticoids, ipratropium, or anti-microbial agents in pulmonary diseases. In patients under mechanical ventilation, the half-life of midazolam (a new benzodiazepine used as a sedative) has been found to be prolonged. And pulmonary absorption of pentamidine was increased in patients under mechanical ventilation. Pharmacokinetic impairment does occur with severe pulmonary diseases and more evidence is needed to understand the exact mechanism and to propose appropriate dosage regimens.
Many PD and PK factors affect the clinical evaluation of respiratory disease drugs. The route of administration and duration of treatment are variables that have impacts on the study outcome. Due to metabolic differences and PD factors, varying results may be obtained relying on whether drugs are orally or intravenously administered. Creative Biolabs has strong abilities to provide various pharmacological assessments to determine the PD characteristics and metabolic profiles of a drug, enabling the most efficient testing protocols for this potential agent.
Fig.1 From prescription to patient health - mapping the medicine to the patient. (Doogue, 2013)
We can provide mature biological models that are independent of the systemic influence on in vivo preparations. Tissue or organ models have been established for studies on respiratory disease drugs (tracheal rings; phrenic diaphragm; pulmonary arterial smooth muscle; lung parenchyma; bronchi).
We can perform varieties of data analysis as required, including PK, drug-drug interaction (DDI), multiple ascending dose (MAD), single ascending dose (SAD), thorough QT (TQT), food effect, etc.
By integrating PD models with pre-clinical data, we can offer probabilistic risk analysis to weed out weak candidates before clinical trials and make the development of respiratory disease drug more efficient.
At Creative Biolabs, our experts take advantage of leading software and other high-end programs to offer the most accurate assessment of critical PD/PK parameters from studies on bioavailability, DDI, food effect, dose escalation, and TQT. We stay informed on latest industry standards and best practices to ensure consistent delivery of timely, detailed, and high-quality analysis reports. Based on dedicated devices and advanced technologies, our clients can obtain comprehensive PK data results and achieve their goals on respiratory disease drug development.
References
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