Abstract：
PURPOSE:To determine by pharmacokinetic (PK) means the role of erythropoietin-receptor (EPO-R) upregulation in fetuses on the elimination of erythropoietin (EPO). MATERIALS AND METHODS:Six fetal sheep were catheterized at a gestational age of 125-127 days and phlebotomized daily for 6 days. Paired tracer PK studies using recombinant human EPO (rHuEPO) were conducted in the sheep fetuses at baseline and post-phlebotomy, 7 days later. A PK model with Michaelis-Menten elimination was simultaneously fit to the PK data at baseline and post-phlebotomy for each fetus. RESULTS:Daily phlebotomies reduced the hemoglobin levels from baseline values of 10.8 (5%) (mean (C.V.)) g/dl to a nadir of 4.5 (17%) g/dl post-phlebotomy. The endogenous EPO concentration rapidly increased after the first phlebotomy and remained elevated, although variable, thereafter. The Michaelis-Menten maximal rHuEPO elimination rate parameter, V(max), was significantly greater post-phlebotomy than at baseline (p < 0.05), increasing 1.31 fold. The fetal baseline "linear" clearance at very low concentrations of rHuEPO was determined to be 117 ml/kg/h, similar to that determined in newborn sheep but 2-3 fold higher than that determined in adult sheep. CONCLUSIONS:The observed increase in V(max) is consistent with an up-regulation of EPO-R due to a positive feedback resulting from the phlebotomy-induced anemia.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Freise KJ,Widness JA,Segar JL,Schmidt RL,Veng-Pedersen Pdoi
10.1007/s11095-007-9295-3subject
Has Abstractpub_date
2007-09-01 00:00:00pages
1653-9issue
9eissn
0724-8741issn
1573-904Xjournal_volume
24pub_type
杂志文章abstract：:The limitations of traditional gas adsorption models for describing water vapor sorption by amorphous pharmaceutical solids are described and an alternative approach based on polymer solution theories is proposed. The approach is tested by comparing a priori predicted isotherms with literature data for the poly(vinylp...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018901325842
更新日期：1993-09-01 00:00:00
abstract：PURPOSE:A series of studies was conducted to evaluate the preclinical pharmacokinetics of SB-239063 (trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-[(2-methoxy)pyrimidin-4-yl] imidazole), a potent and selective p38 MAP kinase inhibitor. METHODS:SB-239063 was administered both i.v. and p.o. in the rat, dog, cynomol...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013002414678
更新日期：2001-09-01 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:To elucidate the apical and basolateral components of the total unstirred water layer in regular permeability experiment. METHODS:A novel stirring apparatus was constructed to remove the basolateral unstirred water layer. Caco-2 cells were used as the permeability barrier both in Transwell-type and side-by-sid...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9573-8
更新日期：2008-07-01 00:00:00
abstract：:Some geminal bisphosphonates are used clinically for a number of important bone/calcium related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bisacylphosphonates (e.g., adipoyl- and suberoylbisphosphonate). These compounds were found to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018956516640
更新日期：1992-01-01 00:00:00
abstract：PURPOSE:Evaluate the ability of (-)-6-aminocarbovir ((-)-6AC) to improve the CNS exposure to (-)-carbovir ((-)-CBV). METHODS:Activation of (-)-6AC in vitro was assessed by incubations of rat brain tissue homogenates. The in vivo brain exposure to (-)-CBV was then examined in rats after iv infusions of either (-)-CBV (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016229624703
更新日期：1995-06-01 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
abstract：PURPOSE:Safe, targeted delivery of therapeutics remains a focus of drug/gene delivery, the aim being to achieve optimal efficacy while minimising off-target delivery. Dendrimers have a vast array of potential applications and have great potential as gene and drug delivery tools. We previously reported the development o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1408-1
更新日期：2014-11-01 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：: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：PURPOSE:The purpose of this study was to evaluate the feasibility of delivering vapreotide, a somatostatin analogue, by transdermal iontophoresis. METHODS:In vitro experiments were conducted using dermatomed porcine ear skin and heat-separated epidermis. In addition to quantifying vapreotide transport into and across ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5276-6
更新日期：2005-08-01 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：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: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:The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. METHODS:Glass microneedles were inserted to a depth of 720-1080 microm into human cadaver skin to mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8498-8
更新日期：2006-01-01 00:00:00
abstract：PURPOSE:To develop a new bionic system from an existing drug dissolution/absorption simulating system (DDASS) to simultaneously predict the release and absorption of enteric-coated formulations. METHODS:In accordance with the pH-dependent characteristics of enteric-coated formulations, the modified DDASS was designed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0905-3
更新日期：2013-02-01 00:00:00
abstract：:Lecithin-stabilized triglyceride emulsions are subject to hydrolysis by pancreatic lipase. The time profiles of these reactions are characterized by a lag-phase and a zero-order phase. Lag phases are more pronounced with long-chain triglycerides. Ca2+ is effective in reducing the lag-phase and activating lipase. Kinet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015956104500
更新日期：1989-06-01 00:00:00
abstract：:Chemoembolization using microspheres of 100- to 200-microns is a useful way to treat primary and secondary hepatic tumors. In a search for a better embolic material, we described in detail the preparation and characterization of a poly(benzyl l-glutamate) (PBLG) microspheres containing cisplatin (CDDP). We determined ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018979703726
更新日期：1994-12-01 00:00:00
abstract：PURPOSE:Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. MATERIALS AND METHODS:In vitro experiments we...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9237-0
更新日期：2007-06-01 00:00:00
abstract：PURPOSE:To characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of a new polyethylene glycol (PEG) conjugate formulation of interferon (IFN)-beta la following subcutaneous (SC) administration in monkeys. METHODS:Single SC injections of 0.3, 1, and 3 million international units (MIU)/kg of PEG-IFN-beta 1...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-9009-z
更新日期：2005-01-01 00:00:00
abstract：PURPOSE:To evaluate micronized powder retention and detachment from inhaler surfaces following reproducible deposition by impaction, coupled with centrifugal particle detachment (CPD). METHODS:Micronized albuterol sulfate (AS) and beclomethasone dipropionate (BDP) were aerosolized as dry powders and deposited by casca...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014451203619
更新日期：2002-03-01 00:00:00
abstract：PURPOSE:To produce and characterize a nonviral ultrasound-controlled release system of plasmid DNA (pDNA) encapsulated in gas-filled poly(D,L-lactide-co-glycolide) microparticles (PLGA-MPs). METHODS:Different cationic polymers were used to form pDNA/polymer complexes to enhance the stability of pDNA during micropartic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014430631844
更新日期：2002-03-01 00:00:00
abstract：:The pharmacokinetics of and biologic response modification by recombinant human interferon-beta ser (rIFN-beta ser) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 x 10(6) IU of rIFN-beta ser followed by a single or eight consecutive daily 90 x 10(6) IU subcuta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018902120023
更新日期：1993-04-01 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: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:Overexpression of hyaluronan (HA) receptors on cancer cells results in enhanced endocytotic uptake of the drug conjugate. An N-(2-hydroxypropyl)methacrylamide (HPMA)-HA polymeric drug delivery system was used for targeted delivery of doxorubicin to cancer cells. METHODS:HA-doxorubicin (DOX) bioconjugates (HA-D...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015170907274
更新日期：2002-04-01 00:00:00
abstract：PURPOSE:The purpose of this study was to investigate the pH-dependent passive and active transport of weakly basic drugs across the human intestinal epithelium. METHODS:The bidirectional pH-dependent transport of weak bases was studied in Caco-2 cell monolayers in the physiologic pH range of the gastrointestinal tract...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1025032511040
更新日期：2003-08-01 00:00:00
abstract：PURPOSE:The purpose of the current study is to evaluate the solubility advantage offered by celecoxib (CEL) amorphous systems and to characterize and correlate the physical and thermodynamic properties of CEL and its amorphous molecular dispersions containing poly(vinylpyrrolidone) (PVP). METHODS:The measurement of cr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000045226.42859.b8
更新日期：2004-10-01 00:00:00
abstract：PURPOSE:Biomaterials which release locally high concentrations of antithrombotic agents should lessen the thrombogenicity of the materials. To evaluate this approach, we prepared novel polyurethane matrices loaded with hirudin and coated them with 2-hydroxyethyl methacrylate (HEMA) by glow discharge plasma deposition (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011987423502
更新日期：1998-05-01 00:00:00
abstract：:The bioavailability of a new sustained-release potassium chloride (KCl) tablet, designed for once-a-day dosing, was compared to a KCl elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016438413297
更新日期：1987-10-01 00:00:00
