Abstract:
:Quantitative structure-activity relationships have long been considered a vital component of drug discovery and development, providing insight into the role of molecular properties in the biological activity of similar and unrelated compounds. Recognition that in vitro bioassay and/or pre-clinical activity are insufficient for anticipating which compounds are suitable leads for further development has shifted the focus toward integrated pharmacokinetic (PK) and pharmacodynamic (PD) processes. Over the last decade, considerable progress has been made in constructing empirical and mechanistic quantitative structure-PK relationships (QSPKR), as well as diverse mechanism-based pharmacodynamic models of drug effects. In this review, traditional and contemporary approaches to developing QSPKR models are discussed, along with selected examples of attempts to couple QSPKR and pharmacodynamic models to anticipate the intensity and time-course of the pharmacological effects of new or related compounds, or quantitative structure-pharmacodynamic relationships modeling. Such models are in accordance with the goals of systems biology and the ideal of designing drugs and delivery systems from first principles.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Mager DEdoi
10.1016/j.addr.2006.08.002subject
Has Abstractpub_date
2006-11-30 00:00:00pages
1326-56issue
12-13eissn
0169-409Xissn
1872-8294pii
S0169-409X(06)00167-0journal_volume
58pub_type
杂志文章,评审abstract::Pulmonary arterial hypertension (PAH) is a rare, but severe and life-threatening disease characterized by vasoconstriction and remodeling of the pulmonary arterioles, leading to progressive increase in pulmonary vascular resistance and ultimately to right-heart failure. In the last two decades, significant progress in...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.06.003
更新日期:2018-08-01 00:00:00
abstract::Modern pharmaceutical delivery systems are intended to produce plasma drug concentration versus time profiles that result in optimum therapeutic efficacy and a minimum of drug concentration-dependent adverse effects. To accomplish this requires that the drug delivery rate and temporal profile be based on the pharmacok...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(98)00028-3
更新日期:1998-09-07 00:00:00
abstract::The description of irregular particle morphology and powder properties may offer unique insights into the performance of materials intended for use in dry powder inhalers. A number of mathematically similar approaches have been used to study these phenomena, all based on evaluating data in terms of irregular oscillati...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00508-5
更新日期:1997-06-09 00:00:00
abstract::New pharmaceutical formulations must be proven as safe and effective before entering clinical trials. Also in the context of pulmonary drug delivery, preclinical models allow testing of novel antimicrobials, reducing risks and costs during their development. Such models allow reducing the complexity of the human lung,...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.10.011
更新日期:2015-05-01 00:00:00
abstract::The early impact of nanotechnology on medicine is beginning to get realized, with novel nanoscale therapeutic and diagnostic modalities under development or in clinical practice today. In this commentary the field of "nanomedicine" is briefly reviewed form the perspective of where we were; where we are today; and wher...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2006.09.011
更新日期:2006-12-01 00:00:00
abstract::The interaction of biological cells with artificial biomaterials is one of the most important issues in tissue engineering and regenerative medicine. The interaction is strongly governed by physical and chemical properties of the materials and displayed with differentiated cellular behaviors, including cell self-renew...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.06.020
更新日期:2018-07-01 00:00:00
abstract::An essential element of tissue homeostasis is the response to injuries, cutaneous wound healing being the most studied example. In the adults, wound healing aims at quickly restoring the barrier function of the skin, leading however to scar, a dysfunctional fibrotic tissue. On the other hand, in fetuses a scarless tis...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.04.011
更新日期:2019-06-01 00:00:00
abstract::Newborn babies can require significant amounts of medication containing excipients intended to improve the drug formulation. Most medicines given to neonates have been developed for adults or older children and contain excipients thought to be safe in these age groups. Many excipients have been used widely in neonates...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/j.addr.2013.11.003
更新日期:2014-06-01 00:00:00
abstract::Endosomes and lysosomes play a critical role in various aspects of cell physiology such as nutrient sensing, receptor recycling, protein/lipid catabolism, and cell death. In drug delivery, endosomal release of therapeutic payloads from nanocarriers is also important in achieving efficient delivery of drugs to reach th...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2016.08.014
更新日期:2017-04-01 00:00:00
abstract::Alexander Fleming's discovery of penicillin heralded an age of antibiotic development and healthcare advances that are premised on the ability to prevent and treat bacterial infections both safely and effectively. The resultant evolution of antimicrobial resistant mechanisms and spread of bacteria bearing these geneti...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.08.003
更新日期:2014-11-30 00:00:00
abstract::Cell surface receptors play a central role in the regulation of both cellular and systemic physiology by mediating intercellular communication, facilitating protein trafficking, and regulating virtually all intracellular processes. Receptor expression is often cell specific and is determined by cellular lineage, genet...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00079-3
更新日期:1998-02-02 00:00:00
abstract::Toll-like receptor 9 (TLR9) agonists have demonstrated substantial potential as vaccine adjuvants, and as mono- or combination therapies for the treatment of cancer and infectious and allergic diseases. Commonly referred to as CpG oligodeoxynucleotides (ODN), TLR9 agonists directly induce the activation and maturation...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2008.12.008
更新日期:2009-03-28 00:00:00
abstract::Safe and effective hemoglobin-based blood substitutes may be advantageous over conventional therapies for certain clinical settings requiring short term blood replacement such as emergency resuscitation and hemodilution in surgery. Many advances have been made in developing these oxygen therapeutics, however safety co...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(99)00050-2
更新日期:2000-02-28 00:00:00
abstract::Over the past few decades, a range of vesicle-based drug delivery systems have entered clinical practice and several others are in various stages of clinical translation. While most of these vesicle constructs are lipid-based (liposomes), or polymer-based (polymersomes), recently new classes of vesicles have emerged t...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.10.012
更新日期:2019-01-01 00:00:00
abstract::Bone metastasis occurs frequently in patients with advanced breast cancer and is a major cause of morbidity and mortality in these patients. In order to advance current therapies, the mechanisms leading to the formation of bone metastases and their pathophysiology have to be better understood. Several in vitro models ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.10.014
更新日期:2014-12-15 00:00:00
abstract::Transferrin receptor has been an important protein for many of the advances made in understanding the intricacies of the intramolecular sorting pathways of endocytosed molecules. The unique internalization and recycling functions of transferrin receptor have also made it an attractive choice for drug targeting and del...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2003.07.004
更新日期:2003-11-14 00:00:00
abstract::The use of liposomes as drug carriers in treatment of various diseases has been explored extensively for more than 20 years. 'Conventional' liposomes, when administered in vivo by a variety of routes, rapidly accumulate in the mononuclear phagocyte system (MPS). The inherent tendency of the liposomes to concentrate in...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(99)00061-7
更新日期:2000-03-30 00:00:00
abstract::Nanomedicine, which is an application of nanotechnologies in healthcare is developed to improve the treatments and lives of patients suffering from a range of disorders and to increase the successes of drug candidates. Within the nanotechnology universe, the remarkable unique and tunable properties of dendrimers have ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.11.007
更新日期:2018-01-01 00:00:00
abstract::Immunotherapy has been widely explored for applications to both augment and suppress intrinsic host immunity. Clinical achievements have seen a number of immunotherapeutic drugs displace established strategies like chemotherapy in treating immune-associated diseases. However, single drug approaches modulating an indiv...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.05.013
更新日期:2017-05-15 00:00:00
abstract::Despite intensive surgical excision, radiation therapy, and chemotherapy, the current life expectancy for patients diagnosed with glioblastoma multiforme is only 12 to 15months. One of the approaches being explored to increase chemotherapeutic efficacy is to locally deliver chemotherapeutics encapsulated within degrad...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2015.04.008
更新日期:2015-08-30 00:00:00
abstract::A pharmaceutical formulation is composed of several formulation factors and process variables. Several responses relating to the effectiveness, usefulness, stability, as well as safety must be optimized simultaneously. Consequently, expertise and experience are required to design acceptable pharmaceutical formulations...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(03)00120-0
更新日期:2003-09-12 00:00:00
abstract::Messenger RNA and small interfering RNA are attractive modalities for curing diseases by complementation or knock-down of proteins. For success of these RNAs, a drug delivery system (DDS) is required to control a pharmacokinetics, to enhance cellular uptake, to overcome biological membranes, and to release the cargo i...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2020.07.001
更新日期:2020-01-01 00:00:00
abstract::The recent introduction of multi-photon microscopy coupled with advances in optics, computer sciences and the available fluorophores used to label molecules of interest have empowered investigators to study the dynamic events within the functioning kidney at cellular and subcellular levels. This emerging technique, wi...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2006.07.017
更新日期:2006-09-15 00:00:00
abstract::Skin pigmentation is a result of melanin produced by melanocytes in the epidermis. Melanocyte activity, along with the type and distribution of melanins, is the main driver for diversity of skin pigmentation. Dark melanin acts to protect against the deleterious effects of ultraviolet (UV) radiation, including photo-ag...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2020.02.002
更新日期:2020-01-01 00:00:00
abstract::Calcium phosphate cements are used as synthetic bone grafts, with several advantages, such as their osteoconductivity and injectability. Moreover, their low-temperature setting reaction and intrinsic porosity allow for the incorporation of drugs and active principles in the material. It is the aim of the present work ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.01.008
更新日期:2012-09-01 00:00:00
abstract::To design an effective particulate drug delivery system having mucoadhesive function, several mucoadhesion tests for polymers and the resultant particulate systems were developed. Mucin particle method is a simple mucoadhesion test for polymers, in which the commercial mucin particles are used. By measuring the change...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2005.07.008
更新日期:2005-11-03 00:00:00
abstract::Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradabil...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2019.09.003
更新日期:2020-01-01 00:00:00
abstract::Cardiovascular functions such as heart rate and blood pressure show 24h variation. The incidence of cardiovascular diseases including acute myocardial infarction and arrhythmia also exhibits diurnal variation. The center of this circadian clock is located in the suprachiasmatic nucleus in the hypothalamus. However, re...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2010.04.011
更新日期:2010-07-31 00:00:00
abstract::Angiogenesis is naturally balanced by many pro- and anti-angiogenic factors while an imbalance of these factors leads to aberrant angiogenesis, which is closely associated with many diseases. Gene therapy has become a promising strategy for the treatment of such a disordered state through the introduction of exogenous...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2016.11.003
更新日期:2017-09-15 00:00:00
abstract::A polymer stereocomplex is defined as a stereoselective interaction between two complementing stereoregular polymers, that interlock and form a new composite, demonstrating altered physical properties in comparison to the parent polymers. The main interactions, resulting in the complexation, are suggested to rely on s...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(03)00042-5
更新日期:2003-04-25 00:00:00