Abstract：
PURPOSE:To determine the pharmacokinetics of GS-522, an oligodeoxynucleotide (GGTTGGTGTGGTTGG) inhibitor of thrombin, after constant infusion and bolus administration in the cynomolgus monkey. METHODS:Using a stability indicating HPLC method, the GS-522 plasma concentration versus time data were obtained after constant infusion (0.1, 0.3, 0.5 mg/kg/min) and bolus administration (11.25 and 22.5 mg/kg). Plasma data after bolus administration was fit to a three-compartment model. RESULTS:The half-lives for the alpha and beta phases were 1.4 and 5.4 min, respectively. Steady state GS-522 concentrations were reached within 10 minutes after initiation of constant infusions. Termination of infusions resulted in a rapid elimination of GS-522 with an average elimination half-life equal to 1.5 min. The Vss calculated from both the constant infusion and bolus data approximated the blood volume of the monkey. Substitution of the phosphodiester backbone at the 3' end of GS-522 with two phosphorothioate linkages did not substantially effect the elimination half-life upon termination of infusion. CONCLUSIONS:These data in conjunction with published biodistribution data suggest that oligodeoxynucleotides are rapidly cleared from plasma by tissue uptake and that little efflux back into blood takes place. Additionally, strategies designed to increase oligodeoxynucleotide resistance to exonucleases will not dramatically increase plasma half-lives.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Lee WA,Fishback JA,Shaw JP,Bock LC,Griffin LC,Cundy KCdoi
10.1023/a:1016295907266subject
Has Abstractpub_date
1995-12-01 00:00:00pages
1943-7issue
12eissn
0724-8741issn
1573-904Xjournal_volume
12pub_type
杂志文章abstract：:The permeation enhancing property of 5% oleic acid in ethanol on beta-estradiol was investigated in vitro and in vivo using symmetrical and asymmetrical side-by-side diffusion cells and the human skin sandwich flap, respectively. beta-Estradiol permeability in vitro and in vivo was similar in 75% ethanol (ETOH). Oleic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018974131236
更新日期：1993-12-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate transepithelial ionic permeation via the paracellular pathway of human Caco-2 epithelial monolayers and its contribution to absorption of the base guanidine. METHODS:Confluent monolayers of Caco-2 epithelial cells were mounted in Ussing chambers and the transepithelial ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9568-2
更新日期：2006-03-01 00:00:00
abstract：PURPOSE:The present study evaluates immobilized artificial membrane (IAM) chromatography for predicting drug permeability across the blood-brain barrier (BBB) and outlines the potential and limitations of IAMs as a predictive tool by comparison with conventional methods based on octanol/water partitioning and octadecyl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011904311149
更新日期：1998-08-01 00:00:00
abstract：:The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016251023427
更新日期：1995-01-01 00:00:00
abstract：:The aim of this investigation was to assess whether immunosuppression induced by total-body irradiation (TBI) affects the pharmacodynamics of centrally acting drugs. Female Sabra rats were exposed to a single dose of gamma irradiation (5.3 Gy). Four days later, when both the cellular and the humoral immune responses w...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018928329824
更新日期：1994-05-01 00:00:00
abstract：PURPOSE:To evaluate the potential of several bis-ester prodrugs of the antiviral agent 9-(2-phosphonylmethoxyethyl)adenine (PMEA, adefovir) to enhance the oral absorption of PMEA. METHODS:Caco-2 monolayers were used to estimate intestinal transport and metabolism of the bis(pivaloyloxymethyl)-ester [bis(POM)-] and a s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011914618109
更新日期：1998-02-01 00:00:00
abstract：PURPOSE:For determination of the transit time through various parts of the gastrointestinal (GI) tract, we developed a method that provides the location of disintegration and drug release. This method involves GI magnetomarkergraphy (GIMG) using a 129-channel Shimadzu vector biomagnetic measurement system (BMS). METHO...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章
doi：10.1023/a:1007561129221
更新日期：2000-02-01 00:00:00
abstract：PURPOSE:The aim was to evaluate fluorescent molecular rotors (DCVJ and CCVJ), which are mainly sensitive to viscosity, for the characterization of polysorbate-containing IgG formulations and compare them to the polarity-sensitive dyes ANS, Bis-ANS and Nile Red. METHODS:IgG formulations with polysorbate 20 or 80 were s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0020-2
更新日期：2010-02-01 00:00:00
abstract：PURPOSE:To determine the effect of Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on the permeation of cromolyn across Caco-2 cell monolayers and explore the molecular basis for the enhanced absorption. METHODS:Transport studies of cromolyn across Caco-2 cell monolayers were conducted in the presence of various ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-7671-9
更新日期：2004-12-01 00:00:00
abstract：:Emulsions (o/w) were prepared from solid-state emulsions comprised of various matrix materials and oils and the resultant particle size properties determined. Results suggest that for those matrices that can form solid-state emulsions, the droplet size decreased as a function of time, as previously observed. The final...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018912100826
更新日期：1993-08-01 00:00:00
abstract：:The influence of the jejunal bloodflow on the absorption of theophylline was investigated. The bloodflow through a segment under investigation was varied by changing the systemic blood pressure by means of a donor blood infusion into the jugular vein or by an infusion of isoprenaline or levarterenol into a femoral vei...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016374508542
更新日期：1984-01-01 00:00:00
abstract：PURPOSE:Within-subject dependency of observations has a strong impact on the evaluation of population pharmacokinetic (PK) and/or pharmacodynamic (PD) models. To our knowledge, none of the current model evaluation tools correctly address this issue. We present a new method with a global test and easy diagnostic plot wh...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0422-9
更新日期：2011-08-01 00:00:00
abstract：PURPOSE:To develop and subsequently evaluate a novel phase inversion-based method used to formulate lipidic nanocapsules. METHODS:Mechanical properties of emulsions prepared by multiinversion phase processes were investigated using a drop tensiometer. Based on the results obtained, a formulation process was developed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016121319668
更新日期：2002-06-01 00:00:00
abstract：:Various diesters of 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) were screened in order to identify a derivative with improved oral absorption. The solubilities and dissolution rates decreased with increasing chain length and branching of the ester group. However, the dipropionate ester showed an anomalously fas...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016462801968
更新日期：1987-04-01 00:00:00
abstract：PURPOSE:To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. METHODS:PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel st...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0875-5
更新日期：2013-02-01 00:00:00
abstract：:Inkjet printing is an attractive material deposition and patterning technology that has received significant attention in the recent years. It has been exploited for novel applications including high throughput screening, pharmaceutical formulations, medical devices and implants. Moreover, inkjet printing has been imp...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-016-1931-3
更新日期：2016-08-01 00:00:00
abstract：PURPOSE:To describe the pharmacokinetics of SK&F 107647, a synthetic hematoregulatory peptide, in healthy volunteers and in patients with adenocarcinoma. METHODS:SK&F 107647 pharmacokinetics were evaluated in 2 dose-escalation studies. Volunteers received SK&F 107647 as single 15-minute iv infusion doses of 1, 10, 100...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007512617139
更新日期：2000-04-01 00:00:00
abstract：:The relationship between pKa and skin irritation in man is studied for a homologous series of benzoic acid derivatives, which permeate through human skin at comparable rates (15-88 micrograms/cm2/hr). Skin irritation and pKa are correlated for pKa less than or equal to 4. Laser Doppler velocimetric assessment of skin ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015931105660
更新日期：1988-10-01 00:00:00
abstract：:Hyaluronan (HA: hyaluronic acid) is produced in the interstitium and reaches the blood circulation through the lymph. It is rapidly eliminated by means of specific receptors on liver endothelium. The elimination characteristics of intravenously administered HA were studied in 10 conscious sheep at the normal plasma HA...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015982204926
更新日期：1989-08-01 00:00:00
abstract：PURPOSE:Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02901-0
更新日期：2020-08-13 00:00:00
abstract：:Solution calorimetry has been employed to evaluate the stability constants and enthalpy changes associated with complex formation between alpha-, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. Data from thermal titrations of the compounds were analyzed using no...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015880218535
更新日期：1991-07-01 00:00:00
abstract：PURPOSE:To test the hypothesis that modification of release pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) formulations shifts gastrointestinal (GI) toxicity of the drugs from the upper GI region to the distal intestine. METHODS:We assessed tiaprofenic acid (TA)-induced upper and lower increased GI permeabil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018887216098
更新日期：1999-01-01 00:00:00
abstract：PURPOSE:The purpose of this study was to evaluate an effect of the proteolytic enzyme papain on permeation of low molecular weight heparin (LMWH) in vitro and in vivo. MATERIALS AND METHODS:In vitro permeation studies were performed using rat small intestine as permeation barrier. In order to determine the ratio of pa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9226-8
更新日期：2007-05-01 00:00:00
abstract：PURPOSE:S-(4-Nitrobenzyl)-6-thioinosine (NBMPR) is routinely used at concentrations of 0.10 μM and 0.10 mM to specifically inhibit transport of nucleosides mediated by equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), respectively. We recently showed that NBMPR (0.10 mM) might also inhibit placental active e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-2782-5
更新日期：2020-02-21 00:00:00
abstract：:The interdependent relationship between pharmacology and toxicology is fundamental to the concepts of efficacy and safety of both drugs and xenobiotics. The traditional concept of establishing efficacious and tolerated doses to define a 'therapeutic window' appears simplistic in the context of an exponentially increas...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-014-1415-2
更新日期：2014-09-01 00:00:00
abstract：PURPOSE:To investigate plasmid DNA interactions with liposomes prepared from dimyristoylglyceroethylphosphocholine (EDMPC) and DOPE using high sensitivity differential scanning calorimetry (HSDSC). MATERIALS AND METHODS:Large unilamellar liposomes of EDMPC with DOPE (mol ratio 0-50%) were prepared. Plasmid DNA was add...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9325-1
更新日期：2007-10-01 00:00:00
abstract：PURPOSE:The objective of this study was to determine the influence of the peptide bond with emphasis on the carbonyl group on the interaction with and transport by the intestinal small-peptide carrier. Therefore enalapril, a known substrate for the small-peptide carrier, has been modified to an analogue with a reduced ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018866611555
更新日期：1999-01-01 00:00:00
abstract：PURPOSE:Drug transfer into milk is a general concern during lactation. Because data are limited in human subjects, particularly for new drugs, experimental animal models of lactational drug transfer are critical. This study analyzed drug transfer into milk in a mouse model, as well as the contribution of similar and di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1085-5
更新日期：2013-09-01 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：:The absorption of insulin across the vaginal mucosa into the systemic circulation was studied in ovariectomized rats given subsequent estrogen treatment. Blood glucose levels were determined as an indirect measure of insulin absorption, and the effect of various enhancers on the hypoglycemic response was investigated....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015892630637
更新日期：1992-07-01 00:00:00
