The incidence of metabolic diseases is increasing all over the world and particularly in advanced countries owing to numerous factors involved. There’s no single effective drug treatment affecting all components of this group of disease yet, and more attention focuses on the new drug discovery, development, and testing. Pharmacodynamics (PD) refers to the relationship between drug concentration at the site of action and the resulting efficacy, including the time course and intensity of therapeutic and adverse effects. As a top-ranking leader in pre-clinical and clinical trials, Creative Biolabs could provide customers with extensive pharmacodynamics services and analysis for metabolic disorders, as well as data management and interpretation for accurate decision making.
Metabolic diseases harbor a cohort of sicknesses, such as obesity and diabetes that belong to one of the fastest growing epidemics worldwide. And most of them showed to contribute towards further cardiovascular, hematological, gastrointestinal, immune disorders, and even oncogenesis. Each component of metabolic diseases has independent goals, thus multiple classes of drugs can be used in the treatment, including weight-loss drugs, antidiabetics, antihypertensives, antilipemic drugs, and so on.
Fig.1 Overview of FDA-approved new molecular entities for metabolic diseases. (Kinch, 2015)
The statistics of new molecular entities (NMEs) against metabolic diseases displays the rate of approval for new drugs increased and still stands at about 2 every year today. This increase is greatly attributed to a current emphasis on the treatments for inborn errors of metabolism. Especially, biological companies have concentrated on rare genetic disorders, often treated with biologic-based NMEs that target novel pathways and qualify for orphan drug roles. In contrast, NMEs development by pharmaceutical companies tended to conventional small molecular targets of nongenetic diseases like diabetes.
The parameter of PD in pharmacy reveals the physiologic, biochemical, and molecular effects of drugs on the body and involves receptor binding, post-receptor effects, and chemical interactions. The metabolic disorder involves a set of risk factors, abdominal obesity, a declined ability to metabolize glucose, hypertension, dyslipidemia, etc. Among them, obesity appears to encompass the largest causal relationship. Recently, there’re two drugs approved for the long-term treatment of obesity. One termed sibutramine (Meridia/Reductil) is a serotonin, dopamine, and norepinephrine reuptake inhibitor that plays centrally to activate anorexigenic signals and block orexigenic signals, and the other termed orlistat (Xenical) is a pancreatic lipase inhibitor that restrains lipolysis and absorption of dietary plasma triglycerides. The pharmacologic response is based on the drug binding to its target, and the drug concentration at the receptor site can influence the drug’s efficacy. The PD of these drugs follow the relationship, Cn x T = h, in which C is drug concentration, T is exposure time, and h is drug exposure constant. The value of n depicts the importance of C and T in determining the drug effect.
Fig.2 Schematic representation of physiology-based pharmacodynamic modeling. (Danhof, 2016)
The PD is not only the means by which drug receptors interact to produce their responses, but also quantifies the drug's effects on individuals and even populations. Understanding the basics of PD benefits to offer an appreciation of considerations underlying drugs used and concentration choices. Creative Biolabs is committed to the development of pre-clinical drug and providing consulting and bioanalytical analyses to drug industry. On top of that, our featured physiology-based pharmacodynamic (PB-PD) modeling services will build a connection between pharmacokinetics (PK) and drug effects on disease progression.
To address PD and PK of drug products in the early development.
PB-PD modeling indicates the processes on the causal path between drug administration and effects, which contains target site distribution, target binding and activation, and transduction and homeostatic feedback.
Once a model constructed, different dosage schemes can be simulated to predict exposure. When clients try to design and justify dosing regimens in clinical trials, this type of service saves valuable resources and times.
There’re many parameters can be tested, including single ascending dose (SAD), multiple ascending doses (MAD), food effect, drug-drug interaction (DDI), thorough QT (TQT), hepatic impaired, renal impaired, site of absorption, radio-labeled mass balance, etc.
In addition to a full report, we also offer PD analyses as required, such as biomarker statistical analysis, quality control of biomarker data, implement statistical analysis, on-demand post-hoc analysis, etc.
Creative Biolabs has always focused on the mechanism of metabolic diseases and devoted to corresponding drug screening and detections. Our clinical pharmacologists have extensive experienced in PK/PD data assessment and would like to propose the most appropriate investigative approach for a specific project. These experts are able to conduct non-compartmental and compartmental PD analyses by data collected from whole blood, plasma, urine, and other biological materials. That results enable clients to evaluate all possible risks of new drugs and help them make informed decisions and timely adjustments for optimal outcomes.
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