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. At the highest dose, a slower third phase with a half-life of 56 min was observed. The total-body clearances were 99, 77, and 37 ml/min-kg for the 8, 40, and 200 mg/kg doses. The steady-state volume of distribution showed a trend for a decrease with increasing doses, but the difference was not statistically significant. Twenty-four-hour urinary recovery of unchanged drug for the three doses was similar at about 20%, suggesting that a major fraction of the dose was metabolized. Urinary excretion of ddI metabolite, hypoxanthine, accounted for less than 5% of the dose. Renal and metabolic clearances decreased with increased doses. ddI was metabolized in blood; the addition of inorganic phosphate, a cosubstrate in phosphorylase-mediated nucleoside catabolism, enhanced the degradation by about fourfold. In summary, these data indicate equal distribution of ddI in the extracellular and intracellular spaces in blood, its enzymatic degradation in blood, and nonlinear elimination kinetics.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Wientjes MG,Mukherji E,Au JLdoi
10.1023/a:1015866714224subject
Has Abstractpub_date
1992-08-01 00:00:00pages
1070-5issue
8eissn
0724-8741issn
1573-904Xjournal_volume
9pub_type
杂志文章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:The purpose of this study was to determine the potential effect of probenecid on the pharmacokinetics of zalcitabine in HIV-positive patients. METHODS:Twelve patients received single oral 1.5 mg doses of zalcitabine alone and during probenecid treatment (500 mg at 8 and 2 hours before and 4 hours after zalcita...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1016009029536
更新日期：1996-03-01 00:00:00
abstract：PURPOSE:The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. METHODS:The impact of sodium taurodeoxycholate (STDC), sodium dodec...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2332-y
更新日期：2018-02-21 00:00:00
abstract：PURPOSE:Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation. Recently, long acting antiretroviral i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1936-y
更新日期：2016-08-01 00:00:00
abstract：PURPOSE:(i) To use trehalose as a model compound to evaluate the concept of crystallinity in pharmaceuticals. (ii) To understand the structural nature of dehydrated trehalose dihydrate. MATERIALS AND METHODS:Trehalose dihydrate was dehydrated isothermally at several temperatures below 100 degrees C and the anhydrous p...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9058-6
更新日期：2006-10-01 00:00:00
abstract：:Many drugs and desirable phytochemicals are bitter, and bitter tastes are aversive. Food and pharmaceutical manufacturers share a common need for bitterness-masking strategies that allow them to deliver useful quantities of the active compounds in an acceptable form and in this review we compare and contrast the chall...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-014-1480-6
更新日期：2014-11-01 00:00:00
abstract：PURPOSE:To develop an isolated perfused rat liver (IPRL) model with low baseline levels of tumor necrosis factor (TNF)-alpha in the outlet perfusate to study the effects of immunostimulants and immunosuppressants on the release of TNF-alpha from this organ. METHODS:Isolated rat livers were perfused with a buffer conta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013603331899
更新日期：2002-01-01 00:00:00
abstract：:Five aliphatic 5'-esters of 5-iodo-2'deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015968113838
更新日期：1988-11-01 00:00:00
abstract：PURPOSE:This study aimed to characterize the transepithelial transport of miltefosine (HePC), the first orally effective drug against visceral leishmaniasis, across the intestinal barrier to further understand its oral absorption mechanism. MATERIALS AND METHODS:Caco-2 cell monolayers were used as an in vitro model of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9170-7
更新日期：2007-03-01 00:00:00
abstract：PURPOSE:To study the PK interaction of L-dopa/benserazide in rats. METHODS:Male rats received a single oral dose of 80 mg/kg L-dopa or 20 mg/kg benserazide or 80/20 mg/kg L-dopa/benserazide. Based on plasma concentrations the kinetics of L-dopa, 3-O-methyldopa (3-OMD), benserazide, and its metabolite Ro 04-5127 were c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1010935228654
更新日期：2001-08-01 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：PURPOSE:The aim of the present study was to improve the dry powder inhalation behavior of steroid KSR-592 with lactose by altering the crystal shape and the particle size of the drug for use in a newly designed inhalation device, Jethaler. METHOD:The shape of the crystals was changed by polymorphic transformation of o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020492213172
更新日期：2002-10-01 00:00:00
abstract：PURPOSE:To monitor the biodistribution of IgG1 aggregates upon subcutaneous (SC) and intravenous (IV) administration in mice and measure their propensity to stimulate an early immune response. METHODS:A human mAb (IgG1) was fluorescently labeled, aggregated by agitation stress and injected in SKH1 mice through SC and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1154-9
更新日期：2014-01-01 00:00:00
abstract：PURPOSE:To assess the efficacy of the novel clinical formulation of fenretinide (LAU-7b) for the treatment of allergic asthma. To study the association between LAU-7b treatment in allergic asthma and the modulation of very long chain ceramides (VLCC). METHODS:We used two allergens (OVA and HDM) to induce asthma in mou...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2743-z
更新日期：2020-01-08 00:00:00
abstract：:Significant efforts are made to characterize molecular liabilities and degradation of the drug substance (DS) and drug product (DP) during various product life-cycle stages. The in vivo fate of a therapeutic protein is usually only considered in terms of pharmacokinetics (PKs) and pharmacodynamics (PDs). However, the ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-019-2689-1
更新日期：2020-01-03 00:00:00
abstract：:Prinomide tromethamine, a nonsteroidal antiinflammatory drug, was orally administered at doses of 250, 500, and 1000 mg every 12 hr for 28 days to healthy male volunteers. The pharmacokinetic behavior of prinomide and its primary plasma metabolite displayed nonlinear characteristics, while those of free prinomide and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018916811904
更新日期：1993-01-01 00:00:00
abstract：PURPOSE:We compared cationic, polyamine-coated microparticles (MPs) and anionic, protein-coated MPs with respect to their phagocytosis and phagosomal fate in dendritic cells (DCs) and macrophages (Mphi). METHODS:Polystyrene MPs were surface modified by covalent coupling with fluorescein isothiocyanate-labeled polyamin...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022271020390
更新日期：2003-02-01 00:00:00
abstract：PURPOSE:Deposition characteristics of MDI and DPI aerosols were compared throughout the conducting airways for the first time using a combination of in vitro experiments and a newly developed stochastic individual path (SIP) model for different inhalation profiles. METHODS:In vitro experiments were used to determine i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0691-y
更新日期：2012-06-01 00:00:00
abstract：:A simple viscometric method was used to quantify mucin-polymer bioadhesive bond strength. Viscosities of 15% (w/v) porcine gastric mucin dispersions in 0.1 N HCl (pH 1) or 0.1 N acetate buffer (pH 5.5) were measured with a Brookfield viscometer in the absence (eta m) or presence (eta t) of selected neutral, anionic, a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015812615635
更新日期：1990-05-01 00:00:00
abstract：PURPOSE:To evaluate the influence of the main biopharmaceutical factors on the viability of a new probiotic yeast strain, using dynamic in vitro systems simulating human gastric/small intestinal (TIM) and large intestinal (ARCOL) environments. METHODS:The viability of Saccharomyces cerevisiae CNCM I-3856 throughout th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0620-5
更新日期：2012-06-01 00:00:00
abstract：PURPOSE:The fate of inhaled salmon calcitonin (sCT) at the respiratory epithelial barrier was studied with particular emphasis on enzymatic degradation by trypsin, chymotrypsin, and neutrophil elastase. METHODS:Degradation of sCT was assessed by HPLC in cell homogenate, supernatant and intact monolayers of human respi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0553-z
更新日期：2012-01-01 00:00:00
abstract：PURPOSE:Present study assessed the influence of gallate esterification on the anti-cancer activity of procyanidin B2 (B2) in androgen-dependent human prostate carcinoma LNCaP cells employing B2-3,3'-di-O-gallate (B2-G(2)), two mono-gallate esters B2-3-O-gallate (B2-3G) and B2-3'-O-gallate (B2-3'G) and the parent compou...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0037-6
更新日期：2010-04-01 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：:The effect of different concentrations of polyvinyl alcohol 14000 and 72000 (PVA 14 and 72) on the activity of betamethasone and phenylephrine hydrochloride in the rabbit eye was investigated. The polymer of higher molecular weight exerts a more pronounced effect at relatively lower viscosities. Effects on the intraoc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016398915965
更新日期：1986-08-01 00:00:00
abstract：PURPOSE:To study epidermal and polyethylene membrane penetration and retention of the sunscreen benzophenone-3 (BP) from a range of single solvent vehicles and evaluate solvent effects on permeability parameters. METHODS:The solubility of BP was measured in a number of solvents. Penetration of BP across human epidermi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011958006973
更新日期：1998-12-01 00:00:00
abstract：PURPOSE:In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products. METHODS:Different sugars as ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1634-1
更新日期：2015-07-01 00:00:00
abstract：:The effects of skin storage, skin preparation, skin pretreatment with a penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4 degrees C...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015822431178
更新日期：1992-03-01 00:00:00
abstract：PURPOSE:To study the physical and release properties of different molecular weight (MW) pH- and temperature-responsive statistical terpolymers and beads of N-isopropylacrylamide (NIPAAm), butylmethacrylate (BMA) and acrylic acid (AA). METHODS:Random terpolymers of varying MW were synthesized with NIPAAm/BMA/AA of feed...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018813700535
更新日期：1999-06-01 00:00:00
abstract：PURPOSE:The purpose of the present study is to explore whether a poly-L-arginine (poly-L-Arg)-induced increase in tight junctions (TJ) permeability of fluorescein isothiocyanate-labeled dextran (MW 4.4 kDa, FD-4) is associated with the Ca2+-dependent signaling and occurs following the phosphorylation/dephosphorylation ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000003383.86238.d1
更新日期：2003-11-01 00:00:00
abstract：PURPOSE:Since a previous qualitative study carried out by us showed the existence of an important influence of the particle size on the percolation thresholds and taking into account that the existing theoretical models can only provide qualitative explanation to this influence, the purpose of this work is to carry out...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016088424993
更新日期：1996-03-01 00:00:00
