Abstract：
PURPOSE:In this study we aimed to evaluate adaptive designs (ADs) by clinical trial simulation for a pharmacokinetic-pharmacodynamic model in oncology and to compare them with one-stage designs, i.e., when no adaptation is performed, using wrong prior parameters. METHODS:We evaluated two one-stage designs, ξ0 and ξ*, optimised for prior and true population parameters, Ψ0 and Ψ*, and several ADs (two-, three- and five-stage). All designs had 50 patients. For ADs, the first cohort design was ξ0. The next cohort design was optimised using prior information updated from the previous cohort. Optimal design was based on the determinant of the Fisher information matrix using PFIM. Design evaluation was performed by clinical trial simulations using data simulated from Ψ*. RESULTS:Estimation results of two-stage ADs and ξ * were close and much better than those obtained with ξ 0. The balanced two-stage AD performed better than two-stage ADs with different cohort sizes. Three- and five-stage ADs were better than two-stage with small first cohort, but not better than the balanced two-stage design. CONCLUSIONS:Two-stage ADs are useful when prior parameters are unreliable. In case of small first cohort, more adaptations are needed but these designs are complex to implement.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Lestini G,Dumont C,Mentré Fdoi
10.1007/s11095-015-1693-3subject
Has Abstractpub_date
2015-10-01 00:00:00pages
3159-69issue
10eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-015-1693-3journal_volume
32pub_type
杂志文章abstract：PURPOSE:The aim was to design and thoroughly characterize monodisperse Fe3O4@SiO2-Ag nanoparticles with strong antibacterial properties, which makes them a candidate for targeting bacterial infections. METHODS:The monodisperse Fe3O4 nanoparticles were prepared by oleic acid-stabilized thermal decomposition of Fe(III) ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2680-x
更新日期：2019-08-14 00:00:00
abstract：PURPOSE:Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques. METHODS:We present a t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1869-5
更新日期：2016-05-01 00:00:00
abstract：:The pharmacokinetics of cefixime, a new orally active cephalosporin, was studied after an intravenous dose of 50 mg/kg to four beagle dogs. Cefixime was shown to exhibit concentration dependent serum protein binding and saturable tubular reabsorption. The drug was excreted mainly in the urine, the net result of glomer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016309923717
更新日期：1986-06-01 00:00:00
abstract：PURPOSE:To study the reaction of artelinic acid with chemical model systems of cytochrome P-450 as a means of obtaining authentic samples of the putative metabolites necessary for identification of the mammalian metabolites of artelinic acid. METHODS:Artelinic acid was reacted with different organic complexes of iron(...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012185124972
更新日期：1997-10-01 00:00:00
abstract：PURPOSE:To investigate the effect of tyrphostin 8 (T-8), a GTPase inhibitor, on transferrin receptor (TfR)-mediated transcytosis of insulin-transferrin (In-Tf) conjugate in cultured enterocyte-like Caco-2 cells and on gastrointestinal (GI) absorption of In-Tf in streptozotocin (STZ)-induced diabetic rats. METHODS:Caco...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011032502097
更新日期：2001-02-01 00:00:00
abstract：PURPOSE:Evidence suggests that uremic toxins such as hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS), and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) promote the progression of renal failure by damaging tubular cells via rat organic anion transporter 1 (rOat1) and rOat3 on the basolateral membrane of ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-2486-x
更新日期：2005-04-01 00:00:00
abstract：PURPOSE:The effects of liposomes on nitric oxide (NO) production from mouse peritoneal macrophages following intraperitoneal injection of liposomes were investigated. METHODS:Mouse peritoneal macrophages were collected following intraperitoneal injection of liposomes and cultured with and without lipopolysaccharide (L...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016034303012
更新日期：1996-09-01 00:00:00
abstract：PURPOSE:The United States Pharmacopoeia (USP) imposes strict requirements on the geometry and operating conditions of the USP Dissolution Testing Apparatus II. A previously validated Computational Fluid Dynamics (CFD) approach was used here to study the hydrodynamics of USP Apparatus II when the impeller was placed at ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9477-z
更新日期：2008-02-01 00:00:00
abstract：PURPOSE:To design and synthesize fatty acid-RGD peptide amphiphiles with ADA linker for their potential delivery of hydrophobic drugs like paclitaxel targeted to α(v)β(3) integrin overexpressing tumors. METHODS:Four amphiphiles - C16 or C18 fatty acid-RGD peptide and ADA linker were designed and synthesized. CMC, size...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0830-5
更新日期：2012-12-01 00:00:00
abstract：PURPOSE:The lack of an in vivo diagnostic test for AD has prompted the targeting of amyloid plaques with diagnostic imaging probes. We describe the development of a contrast agent (CA) for magnetic resonance microimaging that utilizes the F(ab')2 fragment of a monoclonal antibody raised against fibrillar human Abeta42 ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9600-9
更新日期：2008-08-01 00:00:00
abstract：PURPOSE:To investigate the ability of various polymers to inhibit the crystallization of amorphous felodipine from amorphous molecular dispersions in the presence of absorbed moisture. METHODS:Spin coated films of felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9331-3
更新日期：2008-04-01 00:00:00
abstract：PURPOSE:To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection. METHODS:Bupivacaine-containing LPSPs were characterized and optimized in vitro. Male Sprague-Dawley rats were given sciatic nerve blocks with bupivacaine-containing LPSPs....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1026470831256
更新日期：2000-10-01 00:00:00
abstract：:A novel method of dipeptide synthesis is described that can be carried out in aqueous solution and does not require complicated protecting and deprotecting procedures. An analgesic neuropeptide named kyotorphin, H-Tyr-Arg-OH, was synthesized from unprotected tyrosine and arginine in a new enzymatic reaction catalyzed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016479305603
更新日期：1987-04-01 00:00:00
abstract：:Knowledge Management (KM) is a key enabler for achieving quality in a lifecycle approach for production of biopharmaceuticals. Due to the important role that it plays towards successful implementation of Quality by Design (QbD), an analysis of KM solutions is needed. This work provides a comprehensive review of the in...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-016-2043-9
更新日期：2017-02-01 00:00:00
abstract：PURPOSE:To investigate the effect of atomization conditions on particle size and stability of spray-freeze dried protein. METHODS:Atomization variables were explored for excipient-free (no zinc added) and zinc-complexed bovine serum albumin (BSA). Particle size was measured by laser diffraction light scattering follow...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007570030368
更新日期：2000-11-01 00:00:00
abstract：PURPOSE:To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders. METHODS:From a dry powder a fraction of aerosolized particles with an aerodynamic particle size below 5 μm was collected on regenerate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0744-2
更新日期：2012-08-01 00:00:00
abstract：:The application of supercritical fluid (SF) processing in pharmaceutical research is increasing particularly in the field of particle formation for drug delivery systems. The SF processes have benefits over the existing particle formation methods in terms of improved control, flexibility and operational ease. This rev...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1011957512347
更新日期：1999-07-01 00:00:00
abstract：PURPOSE:To examine the inhibitory potential of enalapril [and other angiotensin converting enzyme (ACE) inhibitors] on glycylsarcosine (GlySar) transport by the high-affinity renal peptide transporter. METHODS:Studies were performed in rabbit renal brush border membrane vesicles in which the uptake of radiolabeled Gly...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018847818766
更新日期：1999-05-01 00:00:00
abstract：PURPOSE:The purpose of the study is to characterize glycine crystallization during freezing of aqueous solutions as a function of the glycine salt form (i.e., neutral glycine, glycine hydrochloride, and sodium glycinate), pH, and ionic strength. METHODS:Crystallization was studied by thermal analysis, microscopy, x-ra...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016223101872
更新日期：1995-10-01 00:00:00
abstract：PURPOSE:To test the hypothesis of surface displacement as the underlying mechanism for IgG stabilization by polysorbates and HPβCD against surface-induced aggregation. METHODS:Adsorption/desorption-kinetics of IgG-polysorbate 80/-HPβCD were monitored. Maximum bubble pressure method was used for processes within second...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0854-x
更新日期：2013-01-01 00:00:00
abstract：:Monte Carlo simulation technique used to evaluate the effect of the arrangement of concentrations on the efficiency of estimation of population pharmacokinetic parameters in the preclinical setting is described. Although the simulations were restricted to the one compartment model with intravenous bolus input, they pr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016267811074
更新日期：1995-05-01 00:00:00
abstract：:Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxyester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a "secon...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015973425708
更新日期：1988-08-01 00:00:00
abstract：:New generation vaccines, particularly those based on recombinant proteins and DNA, are likely to be less reactogenic than traditional vaccines but are also less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. Adjuvants can be broadly separated into two classes...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1016104910582
更新日期：2002-06-01 00:00:00
abstract：PURPOSE:The aim was to investigate anticancer drug-loaded poly(carbonate-ester) nanospheres as potential drug delivery systems for cancer therapy. METHODS:Functional poly(carbonate-ester) copolymers (HPCP-SD) were synthesized by the incorporation of sulfadiazine as the tumor-targeting groups to hydroxyl groups of poly...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0275-7
更新日期：2010-12-01 00:00:00
abstract：:A liposomal formulation of methylprednisolone (L-MPL) was developed to improve localization of this immunosuppressant in lymphatic tissues. Liposomes containing MPL were formulated from a mixture of phosphatydylcholine and phosphatydylglycerol (molar ratio, 9:1) and sized by extrusion through a 0.1-micron membrane. Ma...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018954704886
更新日期：1993-10-01 00:00:00
abstract：PURPOSE:In this work, the alacepril thiolesterase, which catalyzes the hydrolyzing reaction of the thiolester linkage in alacepril and the conversion from alacepril to deacetylalacepril, was purified from rat liver cytosol and characterized. METHODS:A purification procedure for the thiolesterase consisted of ammonium ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1025073720126
更新日期：2003-08-01 00:00:00
abstract：PURPOSE:This study was aimed at developing a new active loading method to stably encapsulate staurosporine (STS), a water insoluble drug, into lipid-based nanoparticles (LNPs) for drug targeting to tumors. METHODS:A limited amount of DMSO was included during the active loading process to prevent precipitation and faci...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1854-4
更新日期：2016-05-01 00:00:00
abstract：PURPOSE:Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity. METHODS:An indomethacin hydrolyzing enzyme was purified to homoge...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016061614399
更新日期：1996-09-01 00:00:00
abstract：PURPOSE:Chitosan and its derivatives possess several unique properties relevant in the field of pharmaceutics and medicinal chemistry. This study aimed to evaluate the pharmaceutical performance of an innovative chitosan derivative, methyl acrylate chitosan bearing p-nitrobenzaldehyde (MA*CS*pNBA) Schiff base. METHODS...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2535-x
更新日期：2018-11-07 00:00:00
abstract：PURPOSE:To study the role of unsaturated fatty acid ester substituents in the autoxidation of polysorbate 80 using quantitative kinetics. METHODS:Oxidation kinetics were monitored at 40 degrees C in aqueous solution by tracking head space oxygen consumption using a fiber optic oxygen sensor with phase shift fluorescen...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9946-7
更新日期：2009-10-01 00:00:00
