Abstract:
:Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct compression was then selected for comparison with the commercial oil solution placed into soft gelatin capsules. The study involved a randomized crossover design in six dogs. In order to determine absolute bioavailability and to compensate for any time-dependent changes in clearance, an intravenous tracer dose of 3H-CsA was administered along with each oral test product on each of two occasions. Absolute bioavailability (mean +/- SD) was 46.0 +/- 11.1 and 45.4 +/- 9.9% for the capsules and tablets, respectively. Cmax, tmax, and mean absorption time were not significantly different between the two products. No differences were observed in the pharmacokinetics of the intravenously administered CsA in the two experiments, which were separated by 8-13 days. We conclude that the proposed tablet formulation for CsA is equivalent in dogs to the commercial dosage form placed into soft gelatin capsules.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Abdallah HY,Mayersohn Mdoi
10.1023/a:1015815614959subject
Has Abstractpub_date
1991-04-01 00:00:00pages
518-22issue
4eissn
0724-8741issn
1573-904Xjournal_volume
8pub_type
杂志文章abstract:PURPOSE:To identify the mechanism behind the unexpected bio-performance of two amorphous solid dispersions: BMS-A/PVP-VA and BMS-A/HPMC-AS. METHODS:Solubility of crystalline BMS-A in PVP-VA and HPMC-AS was measured by DSC. Drug-polymer interaction parameters were obtained by Flory-Huggins model fitting. Drug dissoluti...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0695-7
更新日期:2012-10-01 00:00:00
abstract:PURPOSE:To determine the mechanism(s) by which effervescence induces penetration enhancement of a broad range of compounds ranging in size, structure, and other physiocochemical properties across rat and rabbit small intestinal epithelium. METHODS:Effervescent induced penetration enhancement was investigated in vitro ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011936901638
更新日期:1998-06-01 00:00:00
abstract::Photodegradation of solutions of metronidazole in the presence and absence of sodium urate was studied. Photodegradation appeared to follow zero-order kinetics and was found to be dependent on the pH, buffer species, sodium urate concentration, and light source. Complex formation between metronidazole and sodium urate...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015851719579
更新日期:1989-01-01 00:00:00
abstract::Transport studies using intestinal brush-border membrane vesicles isolated from rats and rabbits have failed to demonstrate proton- or Na(+)-dependent carrier-mediated transport of thyrotropin-releasing hormone (TRH), despite a pharmacologically relevant oral bioavailability. To examine the hypothesis that reported le...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018947430018
更新日期:1993-05-01 00:00:00
abstract:PURPOSE:The purpose of the study was to examine the suitability of using laser diffraction to measure the fine particle fraction (FPF) of drugs emitted from carrier-free dry powder aerosol formulations. MATERIALS AND METHODS:Particle size distribution of terbutaline sulphate from Bricanyl Turbohaler, which contained l...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9056-8
更新日期:2006-09-01 00:00:00
abstract:PURPOSE:Polyethylenimine (PEI) is a highly effective gene delivery vector, but because it is an off-the shelf material, its properties may not be optimal. To investigate the effects of the protonation properties of the polymer, we generated PEI derivatives by acetylating varying fractions of the primary and secondary a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000016251.42392.1e
更新日期:2004-02-01 00:00:00
abstract:PURPOSE:Chitosan-based polymeric micelles (CBPMs) are considered as promising carriers for delivery of anticancer drugs, imaging agents and genes. To optimize the physicochemical, pharmaceutical and biological properties of CBPMs, the molecular mechanisms behind the self-assembly behavior of chitosan (CHI) amphiphilic ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1750-y
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:To determine whether a Protected Graft Copolymer (PGC) containing fatty acid can be used as a stabilizing excipient for GLP-1 and whether PGC/GLP-1 given once a week can be an effective treatment for diabetes. METHODS:To create a PGC excipient, polylysine was grafted with methoxypolyethyleneglycol and fatty ac...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0542-2
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:Paclitaxel is active and widely used to treat multiple types of solid tumors. The commercially available paclitaxel formulation uses Cremophor/ethanol (C/E) as the solubilizers. Other formulations including nanoparticles have been introduced. This study evaluated the effects of nanoparticle formulation of pacli...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-4581-4
更新日期:2005-06-01 00:00:00
abstract:PURPOSE:Stable transformants expressing human multidrug resistance 1 (MDR1), monkey MDR1, canine MDR1, rat MDR1a, rat MDR1b, mouse mdr1a, and mouse mdr1b in LLC-PK1 were established to investigate species differences in P-glycoprotein (P-gp, ABCB1) mediated efflux activity. METHODS:The seven cDNAs of MDR1 from five an...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-0285-7
更新日期:2006-07-01 00:00:00
abstract:PURPOSE:A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1619-0
更新日期:2015-07-01 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:The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys. METHODS:Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharm...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007657109012
更新日期:2000-12-01 00:00:00
abstract:PURPOSE:Previous literature has suggested the absence of an effective barrier between the nasal mucosa and the brain for compounds administered via the nasal route. These experiments were conducted to elucidate the role of the blood-brain barrier efflux transporter P-glycoprotein (P-gp) in attenuating delivery of P-gp ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1025053115583
更新日期:2003-08-01 00:00:00
abstract:PURPOSE:Recombinant human platelet glycoprotein Ibalpha-immunoglobulin G1 chimeric proteins (GPIbalpha-Ig) have varying levels of anti-thrombotic activities based on their ability to compete for platelet mediated adhesion to von Willebrand Factor (vWF). Valine substituted GPIbalpha-Ig chimeras, at certain position, inc...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9018-1
更新日期:2006-08-01 00:00:00
abstract:PURPOSE:The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-beta-cyclodextrin (Me(beta)CD) for controlled drug release. METHODS:A hydrophilic model molecule, inulin, was encapsulated within positively charged and ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-4591-2
更新日期:2005-06-01 00:00:00
abstract::The simultaneous diffusion and metabolism of the D- and L-isomers of the aminopeptidase substrate, leucine-p-nitroanilide (LPNA), were examined in vitro in the hamster cheek pouch. L-LPNA was completely hydrolyzed during diffusion across the cheek pouch, whereas D-LPNA crossed the cheek pouch intact. The metabolic bar...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015949614437
更新日期:1989-11-01 00:00:00
abstract:PURPOSE:Calculation of the ideal solubility of a crystalline solute in a liquid solvent requires knowledge of the difference in the molar heat capacity at constant pressure of the solid and the supercooled liquid forms of the solute, delta Cp. Since this parameter is not usually known, two assumptions have been used to...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012148910975
更新日期:1997-05-01 00:00:00
abstract:PURPOSE:TXA9, a novel cardiac glycoside, has a potent anti-proliferative effect against A549 human lung cancer cells, however, possesses a poor water-solubility and a rapid metabolic rate in vivo which limited the further development of TXA9. To overcome the shortcomings of TXA9, four polymer prodrugs of TXA9 were desi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02789-w
更新日期:2020-03-12 00:00:00
abstract::Silk is a remarkable biopolymer with a long history of medical use. Silk fabrications have a robust track record for load-bearing applications, including surgical threads and meshes, which are clinically approved for use in humans. The progression of top-down and bottom-up engineering approaches using silk as the basi...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-018-2534-y
更新日期:2018-11-05 00:00:00
abstract:PURPOSE:Since the molecular mechanism of the cell cycle was established, various theoretical models of this process have been developed. A recent study revealed significant variability in cell cycle duration between mother and daughter cells, but this observation has not been incorporated into the theoretical models. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2570-2
更新日期:2019-02-22 00:00:00
abstract::Equations for the steady-state volumes of distribution (Vss) and the mean residence times in the body (MRT) are derived for a drug and its metabolite subject to reversible metabolism and separately infused intravenously at a constant rate to steady state of both compounds. The Vss and MRT parameters are functions of t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015874329265
更新日期:1990-06-01 00:00:00
abstract:PURPOSE:To point out the importance of heterogeneity in drug distribution processes and develop a noncompartmental approach for the description of the distribution of drug in the body. METHODS:A dichotomous branching network of vessels for the arterial tree connected to a similar venous network was used to describe th...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016031129053
更新日期:1996-05-01 00:00:00
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:To investigate the destruction of clinically-relevant bacteria within biofilms via the sustained release of the antibiotic tetracycline from zein-based electrospun polymeric fibrous matrices and to demonstrate the compatibility of such wound dressing matrices with human skin cells. METHODS:Zein/PCL triple laye...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1782-3
更新日期:2016-01-01 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::The stability of a freeze-dried model protein, ribonuclease A (RNase), was investigated under accelerated storage conditions at 45 degrees C for time periods up to 60 days. Because RNase is a fairly stable molecule around pH 7, lyophilization was performed in phosphate buffers at pH 4.0 or 10.0 to accelerate degradati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015959604616
更新日期:1990-10-01 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::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:Studies were conducted to investigate dilute solutions of the monoclonal antibody (mAb) bevacizumab, mAb fragment ranibizumab and fusion protein aflibercept, develop common procedures for formulation of low concentration mAbs and identify a stabilizing formulation for anti-VEGF mAbs for use in in vitro permeati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2368-7
更新日期:2018-02-28 00:00:00