Abstract:
INTRODUCTION:Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships. AREAS COVERED:In this review, the authors discuss tools that are utilized to describe and predict the PK/PD features of therapeutic proteins and that are valuable additions in the armamentarium of drug development approaches to facilitate and accelerate their successful preclinical and clinical development. EXPERT OPINION:A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Diao L,Meibohm Bdoi
10.1517/17425255.2015.1041917subject
Has Abstractpub_date
2015-07-01 00:00:00pages
1115-25issue
7eissn
1742-5255issn
1744-7607journal_volume
11pub_type
杂志文章,评审abstract:INTRODUCTION:Nucleosidic analogs such as pyrimidine and purine derivatives are mainstay in the field of treating cancers, both in adults and in children. All these drugs act as antimetabolite compounds, that is, they interfere with the ability of cancer cells to synthesize the nucleosides or the nucleotides necessary f...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.985648
更新日期:2015-05-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:There has been much interest in generating gene signatures to predict treatment response in breast cancer. AREAS COVERED IN THIS REVIEW:There are at least 15 published studies that describe baseline tumor gene signatures predicting chemotherapy sensitivity. As an extension of these baseline stu...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903510611
更新日期:2010-03-01 00:00:00
abstract:INTRODUCTION:Within recent years, glucagon-like peptide 1 receptor agonists (GLP-1-RA) have emerged as a new treatment option for type 2 diabetes. The GLP-1-RA are administered subcutaneously and differ substantially in pharmacokinetic profiles. AREAS COVERED:This review describes the pharmacokinetics and safety aspec...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.731394
更新日期:2013-01-01 00:00:00
abstract::Irritable bowel syndrome (IBS) is a chronic disease characterized by complex interactions between genetic predisposition and the environment. Current treatments for IBS are characterized by a highly variable response. Gene variations may result from insertions or deletions, gene rearrangements, splice variants or copy...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 社论
doi:10.1517/17425255.2015.1048223
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Therapeutic hypothermia is being employed clinically due to its neuro-protective benefits. Both critical illness and therapeutic hypothermia significantly affect drug disposition, potentially contributing to drug-therapy and drug-disease interactions. Currently, there is limited information on the known al...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.574127
更新日期:2011-07-01 00:00:00
abstract:INTRODUCTION:Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain management treatment is currently available. AREAS COVERED:The origin of PDN is enigmatic, and t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1184648
更新日期:2016-07-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:many promising targeted agents and combination therapies are being investigated for brain cancer. However, the results from recent clinical trials have been disappointing. A better understanding of the disposition of drug in the brain early in drug development would facilitate appropriate channe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2010.523420
更新日期:2010-12-01 00:00:00
abstract:INTRODUCTION:There have been increasing concerns regarding adverse reactions and toxicity incidents caused by traditional Chinese medicines (TCMs), among which the nephrotoxicity is particularly worrying. AREAS COVERED:This review summarizes the ingredients with renal toxicity from some TCMs through searching the rele...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1132306
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:A major challenge in transplantation is improving long-term organ transplant and patient survival. Immunosuppressants protect the transplant organ from alloimmune reactions, but sometimes also exhibit limiting side effects. The key to improving long-term outcome following transplantation is the selection o...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.544249
更新日期:2011-02-01 00:00:00
abstract:INTRODUCTION:The pharmacokinetic properties of anti-infective drugs are a determinant part of treatment success. Pathogen replication is inhibited if adequate drug levels are achieved in target sites, whereas excessive drug concentrations linked to toxicity are to be avoided. Anti-infective distribution can be predicte...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1037278
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Topotecan was initially approved for the treatment of recurrent ovarian cancer. In cervical cancer, it has been investigated for its potential as part of systemic therapy for advanced and/or recurrent disease and in combination with cisplatin and radiation as a first-line treatment for advanced disease. As...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.758249
更新日期:2013-02-01 00:00:00
abstract:INTRODUCTION:Idiosyncratic drug-induced agranulocytosis (IDIAG) is a life-threatening adverse reaction characterized by an absolute neutrophil count < 500 cells/μl of blood. It shares many of the characteristics of other idiosyncratic drug reactions (IDRs), and this presumably reflects mechanistic similarities. AREAS ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.985649
更新日期:2015-02-01 00:00:00
abstract::Introduction: Overactive bladder (OAB) has a heterogeneous presentation that varies between individuals and by gender. Treatment with antimuscarinic medications is standard first line pharmacotherapy for most patients with OAB. However, gender specific differences in the pharmacokinetics and pharmacodynamics of antimu...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1714591
更新日期:2020-02-01 00:00:00
abstract::Rats are an important tool in pharmacology and toxicology. The authors focus on rat P450s in relation to diazepam metabolism. In particular, considerable attention is devoted to the CYP2D subfamily, which is a group of highly polymorphic enzymes. First, the metabolic profiles of diazepam of humans and other animals ar...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903207002
更新日期:2009-11-01 00:00:00
abstract::Introduction: Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplantation (HSCT); therefore, the prevention of GVHD is important for a successful treatment. Tacrolimus (Tac), a calcineurin inhibitor, has been widely used for the prophylaxis of GVHD in HSCT recipients. Ar...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1675635
更新日期:2019-10-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Cytochrome (CYP) P450 is a collective name for a very large group of heme enzymes, which catalyze largely oxidative reactions, including those of pharmacological and toxicological importance. Their efficient operation requires coupling of specific electron donor and O(2) consumption and substrat...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903329095
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Apigenin, a natural flavone, is widely distributed in plants such as celery, parsley and chamomile. It is present principally as glycosylated in nature. Higher intake of apigenin could reduce the risk of chronic diseases. It has gained particular interest in recent years as a beneficial, health-promoting a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1251903
更新日期:2017-03-01 00:00:00
abstract:INTRODUCTION:Oral mucositis, one of the major side effects of chemotherapy and irradiation, is still a burden of modern oncology. The keratinocyte growth factor (KGF) palifermin has been approved as a new, targeted therapy for the prevention of severe oral mucositis. AREAS COVERED:The authors review the literature on ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.566556
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND:5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the treatment of UC. OBJECTIVE:To summarize current data on balsalazide and to discuss its impact on management of UC. METHODS:A systematic review o...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903206996
更新日期:2009-10-01 00:00:00
abstract:INTRODUCTION:Luteinizing hormone-releasing hormone agonists such as leuprolide acetate (LA) are the most frequently utilized treatment of advanced prostate cancer as the regimen for achieving androgen deprivation therapy (ADT). The efficacy of LA is determined by extent of testosterone (T) suppression in prostate cance...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1073711
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Recent advances in molecular biology have enabled personalized cancer therapies with molecularly targeted agents (MTAs), which offer a promising future for cancer therapy. Dynamic modeling and simulation (M&S) is a powerful mathematical approach linking drug exposures to pharmacological responses, providin...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1141895
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclon...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1417388
更新日期:2018-01-01 00:00:00
abstract:INTRODUCTION:Drug-induced cholestasis, intrahepatic cholestasis of pregnancy and viral hepatitis are acquired forms of liver disease. Cholestasis is a pathophysiologic state with impaired bile formation and subsequent accumulation of bile salts in hepatocytes. The bile salt export pump (BSEP) (ABCB11) is the key export...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.557067
更新日期:2011-04-01 00:00:00
abstract:INTRODUCTION:Gestational diabetes mellitus (GDM) complicates 10% of all pregnancies and is defined as hyperglycemia first noted during pregnancy. Rates of GDM are rising and untreated GDM results in complications for both mother and fetus. GDM is often managed by diet and exercise but 30-40% of women will require pharm...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1187131
更新日期:2016-06-01 00:00:00
abstract:INTRODUCTION:The N-acetylation polymorphism has been the subject of comprehensive reviews describing the role of arylamine N-acetyltransferase 2 (NAT2) in the metabolism of numerous aromatic amine and hydrazine drugs. AREAS COVERED:We describe and review data that more clearly defines the effects of NAT2 haplotypes an...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2021.1840551
更新日期:2021-01-01 00:00:00
abstract:INTRODUCTION:Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. AREAS COVERED:The purpose of this work is to critically review original data as well as previous reviews an...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2021.1836157
更新日期:2021-01-01 00:00:00
abstract:INTRODUCTION:Telaprevir is one of the first direct-acting antiviral drugs approved for the treatment of the hepatitis C virus (HCV) genotype 1. Following its approval in 2011, new data regarding the pharmacokinetics and pharmacodynamics were reported, leading to important clinical applications. AREAS COVERED:This arti...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1049532
更新日期:2015-07-01 00:00:00
abstract::There is an increasing recognition within the pharmaceutical industry of the importance of the ADME studies in drug registration. Consequently, there has been a drive in recent times to conduct the ADME studies as early as possible in the development programme. There are, however, regulatory barriers, particularly in ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.1.23
更新日期:2005-06-01 00:00:00
abstract:INTRODUCTION:Mathematical models of dermal transport offer the advantages of being much faster and less expensive than in vitro or in vivo studies. The number of methods used to create such models has been increasing rapidly, probably due to the steady rise in computational power. Although each of the various approache...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1063615
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:To investigate the metabolic routes and metabolites of myricitrin, an important active ingredient of traditional herbal medicine, yielded by the isolated human intestinal bacteria, which have not been reported previously. METHODS:Fresh human fecal samples were collected from a healthy female volunteer and ab...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1517/17425255.2014.918954
更新日期:2014-07-01 00:00:00