Abstract：
:Assessment of bioavailability/bioequivalence generally relies on the comparison of rate and extent of drug absorption between products. Rate of absorption is commonly expressed by peak concentration (C(max)) and time to peak concentration (T(max)), although these parameters are indirect measures of absorption rate. Recognizing the importance of systemic exposure to drug efficacy and safety, FDA recommended that systemic exposure be better used for bioavailability/bioequivalence assessment. Apart from peak exposure and total exposure, FDA also recommended a new metric for early exposure that is considered necessary when a control of input rate is critical to ascertain drug efficacy and/or safety profile. The early exposure can be measured by truncating the area under the curve at T(max) of the reference product (PAUC(r,tmax)) or some designated early time after dosing. The choice of truncation is most appropriately based on PK/PD relationship or efficacy/safety data for the drug under examination. Compared with C(max), PAUC(r,tmax) has higher sensitivity in detecting formulation differences and may be more variable. If the metric is highly variable, the reference-scaling approach can be employed for bioequivalence evaluation. The partial area metric is useful in PK/PD characterization as well as in the evaluation of bioavailability, bioequivalence and/or comparability.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Chen ML,Davit B,Lionberger R,Wahba Z,Ahn HY,Yu LXdoi
10.1007/s11095-011-0421-xsubject
Has Abstractpub_date
2011-08-01 00:00:00pages
1939-47issue
8eissn
0724-8741issn
1573-904Xjournal_volume
28pub_type
杂志文章,评审abstract：PURPOSE:To examine and determine the sites and the kinetics of IgG1 mAb modifications from both in vitro (rat plasma and PBS) and in vivo (rat model) time-course studies. METHODS:A comprehensive set of protein characterization methods, including RPLC/MS, LC-MS/MS, iCIEF, capSEC, and CE-SDS were performed in this repor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0860-z
更新日期：2013-01-01 00:00:00
abstract：PURPOSE:This study addresses the effect of freezing and thawing on a therapeutic monoclonal antibody (mAb) solution and the corresponding buffer formulation. Particle formation, crystallization behaviour, morphology changes and cryo-concentration effects were studied after varying the freezing and thawing rates, buffer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2378-5
更新日期：2018-03-19 00:00:00
abstract：PURPOSE:The purpose of the present study was to use the human colorectal carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying the effects of cyclodextrins as absorption enhancers. METHODS:Cyclodextrins of varying sizes and physicochemical characters were investigated. The effects of the cyc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016225707807
更新日期：1995-09-01 00:00:00
abstract：PURPOSE:To elucidate the key parameters affecting solute transport from semi-interpenetrating networks (sIPNs) comprised of poly(ethylene glycol) diacrylate (PEGdA) and gelatin that are partially crosslinked, water-swellable and biodegradable. Effects of material compositions, solute size, solubility, and loading densi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9923-1
更新日期：2009-09-01 00:00:00
abstract：PURPOSE:Basal insulins with improved kinetic properties can potentially be produced using acylation by fatty acids that enable soluble, high-molecular weight complexes to form post-injection. A series of insulins, acylated at B29 with fatty acids via glutamic acid spacers, were examined to deduce the structural require...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0739-z
更新日期：2012-08-01 00:00:00
abstract：PURPOSE:For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of ae...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1992-3
更新日期：2016-11-01 00:00:00
abstract：PURPOSE:To measure the charge to mass (Q/M) ratios of the impactor stage masses (ISM) from commercial Flixotide™ 250 μg Evohaler, containing fluticasone propionate (FP), Serevent™ 25 μg Evohaler, containing salmeterol xinafoate (SX), and a combination Seretide™ 250/25 μg (FP/SX) Evohaler metered dose inhalers (MDIs). M...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2544-9
更新日期：2018-11-26 00:00:00
abstract：PURPOSE:Synthetic hydrogels fabricated from photopolymerization are attractive for tissue engineering for their controlled macroscopic properties, the ability to incorporate biological functionalities, and cell encapsulation. The goal of the present study was to exploit the attractive features of synthetic hydrogels to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9619-y
更新日期：2008-10-01 00:00:00
abstract：PURPOSE:We examined the ability of a protein transduction domain (PTD), YARA, to penetrate in the skin and carry a conjugated peptide, P20. The results with YARA were compared to those of a well-known PTD (TAT) and a control, nontransducing peptide (YKAc). The combined action of PTDs and lipid penetration enhancers was...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-2591-x
更新日期：2005-05-01 00:00:00
abstract：PURPOSE:Many genetic disorders, including chondrodysplasias, and acquired disorders impair growth plate function, resulting in short and sometimes malformed bones. There are multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate, which could potentially be used to treat these disorders...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1636-z
更新日期：2015-07-01 00:00:00
abstract：:One of the authors has his name incorrectly indexed in PubMed and SpringerLink as "Laird Forrest M" (last name "Laird Forrest"). His name should index as "Forrest M. Laird" with last name as "Forrest". ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,已发布勘误
doi：10.1007/s11095-018-2463-9
更新日期：2018-07-25 00:00:00
abstract：PURPOSE:To describe a computational tool to calculate molecular descriptors of potential application in ADME virtual screening of antitumor Pt(II) drug candidates. METHODS:The multistep computational procedure consists in (a) building and optimization (PM3) of the 3D structures of the investigated complexes, (b) param...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0317-1
更新日期：2011-03-01 00:00:00
abstract：UNLABELLED:PURPOSE; The aim of this study was to investigate asparagine (Asn) deamidation and aspartate (Asp) isomerization and to measure the content of isoaspartate (isoAsp) in recombinant human interleukin-11 (rhIL-11). METHODS:The rhIL-11 control and heat stressed samples were characterized with trypsin and endopr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1019814713428
更新日期：2002-08-01 00:00:00
abstract：PURPOSE:The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. METHODS:The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in li...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2209-0
更新日期：2017-10-01 00:00:00
abstract：PURPOSE:Pluronics are known as inhibitors of multidrug resistance thus making tumor cells sensitive to therapeutic doses of drugs. The purpose of our study consists in revealing molecular targets of the hydrophobic poly(propylene oxide) block of pluronics in living cells and the dependence of the polymers chemosensitiz...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2484-4
更新日期：2018-09-06 00:00:00
abstract：PURPOSE:In principle, maximum transepidermal fluxes of solutes should be similar for different vehicles, except when the solute or vehicle modifies the skin. Here we estimated maximum flux, stratum corneum solubility, diffusivity and permeability coefficient for a range of similarly sized phenolic compounds with varyin...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0846-x
更新日期：2013-01-01 00:00:00
abstract：PURPOSE:Excipients are added to lyophilized protein drug formulations to protect the protein during processing and storage, but the mechanisms are poorly understood. Here, hydrogen/deuterium (H/D) exchange with mass spectrometry was used to assess protein conformation and excipient interactions in lyophilized solids. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9365-6
更新日期：2008-02-01 00:00:00
abstract：OBJECTIVES:We recently demonstrated that fibrin-based tissue engineered blood vessels (TEV) exhibited vascular reactivity, matrix remodeling and sufficient strength for implantation into the veins of an ovine animal model, where they remained patent for 15 weeks. Here we present an approach to improve the mechanical pr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9499-6
更新日期：2008-05-01 00:00:00
abstract：:Nanotechnology has continuously contributed to the fast development of diagnostic and therapeutic agents. Theranostic nanomedicine has encompassed the ongoing efforts on concurrent molecular imaging of biomarkers, delivery of therapeutic agents, and monitoring of therapy response. Among these formulations, polymer-bas...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-013-1103-7
更新日期：2014-06-01 00:00:00
abstract：:Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects ~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influenc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0951-x
更新日期：2013-03-01 00:00:00
abstract：:The three-dimensional structures and molecular electrostatic potentials of the cis(Z) and trans(E)-isomers of flupenthixol and clopenthixol were examined by computer graphics and molecular mechanical and quantum mechanical calculations, and their internal molecular motions were studied by molecular dynamics simulation...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015842926345
更新日期：1991-04-01 00:00:00
abstract：:The pharmacokinetics of 2',3'-dideoxyinosine (ddI) were examined in rats given intravenous doses of 8, 40, or 200 mg/kg. The concentrations of ddI in whole blood and plasma were identical. The concentration decline was multiexponential, with mean half-lives of 2 and 20 min for the first and second phases, respectively...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015866714224
更新日期：1992-08-01 00:00:00
abstract：:One of the barriers to transdermal delivery of peptides is the metabolic activity of the epidermis. To define this metabolic activity, aminopeptidase activity and Leu-enkephalin metabolism were measured in the epidermis obtained from neonatal mouse skin and in cultured mouse keratinocytes. Aminopeptidase activity was ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015882323677
更新日期：1991-01-01 00:00:00
abstract：PURPOSE:To evaluate and classify the hydrolases of the primate lung. METHODS:Homologous series of aromatic, aliphatic, and choline ester substrates were assayed with the pH-stat method to obtain the Michaelis-Menten kinetic constants, Vmax and K(m), for the enzymes in pulmonary alveolar tissue with esterase activity. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012004911942
更新日期：1997-02-01 00:00:00
abstract：PURPOSE:To assess the effects of selective lipid extraction and tape stripping on transepidermal water loss (TEWL) at three body regions in the pig. METHODS:Lipids were extracted from the abdominal, inguinal. and back regions using three different solvent extraction procedures or cellophane tape stripping (15x) on Yor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1010944529387
更新日期：2001-07-01 00:00:00
abstract：PURPOSE:The purpose of this work was to investigate the mechanisms of cocrystal formation during cogrinding and storage of solid reactants, and to establish the effects of water by cogrinding with hydrated form of reactants and varying RH conditions during storage. METHODS:The hydrogen bonded 1:1 carbamazepine-sacchar...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9110-6
更新日期：2006-10-01 00:00:00
abstract：PURPOSE:To evaluate the reaction of a large series of pharmacologically significant 1,4-dihydropyridine (1,4-DHP) compounds with superoxide (O2.-) in dimethylsulfoxide using differential pulse voltammetry and controlled potential electrolysis. METHODS:Differential pulse voltammetry was used to track the consumption of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022291624933
更新日期：2003-02-01 00:00:00
abstract：PURPOSE:Adenoviruses are being developed for diseases of the gastrointestinal tract. Several in vitro assays were used to predict stability of PEGylated adenovirus along the GI tract and determine in vivo gene transfer after oral administration. METHODS:Recombinant adenovirus was modified with monomethoxypoly(ethylene...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1025714412337
更新日期：2003-09-01 00:00:00
abstract：PURPOSE:Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. METHODS:In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tob...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1361-z
更新日期：2014-10-01 00:00:00
abstract：PURPOSE:The feasibility of using iontophoresis to enhance the permeation rate of a model peptide was investigated in vitro using hairless mouse skin. METHODS:Angiotensin 2 (AT 2) was employed as a permeant probe, using optimum iontophoresis conditions. A number of physicochemical parameters (donor ionic strength; vale...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016254230155
更新日期：1995-07-01 00:00:00
