Abstract：
:The influence of varying protein and fat content in milk of New Zealand White rabbits on the milk-to-plasma drug concentration (M/P) ratio of diazepam was studied. At various time points after littering, a bolus dose (1.5 mg/kg) followed by a 26-hr infusion (1.8 mg/h) of diazepam was administered to freely moving rabbits via a jugular vein catheter. Milk and blood samples were collected to allow characterization of milk composition and quantitative determination of diazepam and nordazepam in milk and plasma. At steady state diazepam showed M/P ratios between 3.7 and 9.5, whereas nordazepam showed ratios between 2.1 and 4.3, respectively. The relative importance of milk protein binding and milk-fat partitioning for the excretion of a drug into milk depended on the drug's affinity to milk fat. A stepwise multiple regression analysis suggested that observed M/P ratios of diazepam could be explained by considering the fat content of milk alone. Nordazepam with a lower solubility in milk fat showed M/P ratios which could be best explained by considering protein and fat concentrations together. Using the data from the infusion studies, two recently published diffusional models to predict M/P ratios were evaluated. Neither model could accurately predict the M/P ratios of diazepam and nordazepam observed in rabbits. However, after extending the model described by Atkinson and Begg to take the actually measured partitioning between skim milk and milk fat into account, a great improvement in the predictive power for observed M/P ratios occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Stebler T,Guentert TWdoi
10.1023/a:1015809418284subject
Has Abstractpub_date
1992-10-01 00:00:00pages
1299-305issue
10eissn
0724-8741issn
1573-904Xjournal_volume
9pub_type
杂志文章abstract：:The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent wi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015834114359
更新日期：1991-12-01 00:00:00
abstract：:Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction pa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018973530443
更新日期：1993-06-01 00:00:00
abstract：PURPOSE:It was the purpose of this study to develop a new oral drug delivery system for low molecular weight heparin (LMWH) providing an improved bioavailability and a prolonged therapeutic effect. METHODS:The permeation enhancing polycarbophil-cysteine conjugate (PCP-Cys) used in this study displayed 111.4 +/- 6.4 mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023803706746
更新日期：2003-06-01 00:00:00
abstract：PURPOSE:To demonstrate that polyanhydride copolymer chemistry affects the uptake and intracellular compartmentalization of nanospheres by THP-1 human monocytic cells. METHODS:Polyanhydride nanospheres were prepared by an anti-solvent nanoprecipitation technique. Morphology and particle diameter were confirmed via scan...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9760-7
更新日期：2009-03-01 00:00:00
abstract：PURPOSE:Recently identified organic solute transporter (Ost) alpha and beta are located on the basolateral membrane of enterocytes and may be responsible for the intestinal absorption of many substrates including bile acids. In the present study, the mechanism governing the transcriptional regulation of their expressio...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9163-6
更新日期：2007-02-01 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：:Cholinesterases are ubiquitous carboxylesterase type B enzymes capable of hydrolyzing the neurotransmitter acetylcholine which are transiently expressed in multiple germline, embryonic, and tumor cells. The acute poisoning effects of various organophosphorous compounds are generally attributed to their irreversible co...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1015867021628
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHAD® adjuvant. METHODS:Virosomes were initially formed by contacting a lipid film containing 3D-PHAD® with viral membranes s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2453-y
更新日期：2018-07-03 00:00:00
abstract：:The effect of γ-cyclodextrin and its four derivatives on the solubility of progesterone in phosphate buffer pH 7.4 was investigated. γ-Cyclodextrin forms a complex precipitating from solution at low cyclodextrin concentrations. No precipitation of complexes was observed with the γ-cyclodextrin derivatives. This change...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016301919928
更新日期：1985-11-01 00:00:00
abstract：PURPOSE:This paper aims to investigate the immunoinhibitory properties of a lymph nodes-targeting suppressive oligonucleotide (ODN) for the potential treatment of autoimmune diseases or chronic inflammation. METHODS:Synthetic suppressive ODN engineered with an albumin-binding diacyl lipid at the 5'-terminal (lipo-ODN)...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2344-2
更新日期：2018-02-08 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:An asymmetric membrane (AM) tablet was developed for a soluble model compound to study the in vitro drug release mechanisms in challenge conditions, including osmotic gradients, concentration gradients, and under potential coating failure modes. Porous, semipermable membrane integrity may be compromised by a hi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9142-y
更新日期：2007-02-01 00:00:00
abstract：PURPOSE:Using monolayers of human pancreatic adenocarcinoma cells (Panc-1) that express multidrug resistance-associated protein (MRP), the present work investigates the effects of Pluronic block copolymers on the functional activity of MRP. METHODS:The studies examined the accumulation and efflux of the MRP selective ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018873702411
更新日期：1999-03-01 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: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：PURPOSE:Highly lipophilic basic drugs, the antiestrogens AE 1 (log P = 5.82) and AE 2 (log P = 7.8) shall be delivered transdermally. METHODS:Transdermal permeation of drugs, enhancers, and solvents from various fluid formulations were characterized by in-vitro permeation studies through excised skin of hairless mice....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015314314796
更新日期：2002-05-01 00:00:00
abstract：PURPOSE:PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) is an excellent biomaterial for tissue repair. Here, we aim to develop a PHBHHx-based three-dimensional (3D) scaffold system for sustained delivery of proteins (insulin serves as a model protein). METHODS:The insulin-phospholipid complex (INS-PLC) was prep...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0944-9
更新日期：2013-04-01 00:00:00
abstract：:The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015954609527
更新日期：1989-04-01 00:00:00
abstract：:The efficacy of topical formulations of acidic fibroblast growth factor (aFGF) in healing of full-thickness wounds has been studied in a diabetic db+/db+ mouse model. The effect of several formulation variables, dose, and application frequency was examined. It was found that wound healing in diabetic animals treated w...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018993610801
更新日期：1994-01-01 00:00:00
abstract：:Intranasal route continues to be one of the main focuses of drug delivery research. Although it is generally perceived that the nasal route could avoid the first-pass metabolism in liver and gastrointestinal tract, the role of metabolic conversions in systemic and brain-targeted deliveries of the parent compounds and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0127-5
更新日期：2010-07-01 00:00:00
abstract：PURPOSE:Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. MET...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1887-3
更新日期：2016-06-01 00:00:00
abstract：PURPOSE:The gastric mucoadhesive property of tetracycline-sucralfate acidic complex (CO) was evaluated by using a novel method in vitro to compare with the in vivo test. The mucoadhesive mechanism of the acidic complex was also studied. METHODS:The gastric mucosa removed from a rat was placed covering the end of a plu...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/B:PHAM.0000019293.57927.7f
更新日期：2004-03-01 00:00:00
abstract：PURPOSE:Type I collagen accumulates during liver fibrosis primarily because α-complex protein-2 (αCP(2)), encoded by the poly(rC) binding protein 2 (PCBP2) gene, binds to the 3' end of the collagen mRNA and increases its half-life. This study aimed to reverse the pro-fibrogenic effect of alcohol on hepatic stellate cel...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0475-9
更新日期：2011-12-01 00:00:00
abstract：:Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multipl...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-017-2333-x
更新日期：2018-02-15 00:00:00
abstract：:The transient dynamic swelling and dissolution behavior during the release of a growth hormone releasing peptide, [D-Trp2-D-Phe5]GHRP, from erodible, non-cross-linked poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads has been investigated at pH 7.4 as a function of buffer concentration. Although the swell...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018902404036
更新日期：1993-07-01 00:00:00
abstract：PURPOSE:This study addresses the effect of freezing and thawing on a therapeutic monoclonal antibody (mAb) solution and the corresponding buffer formulation. Particle formation, crystallization behaviour, morphology changes and cryo-concentration effects were studied after varying the freezing and thawing rates, buffer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2378-5
更新日期：2018-03-19 00:00:00
abstract：:A two-step analytic procedure to determine the rate and extent of metabolite production following administration of the parent compound is described. The procedure provides the rate and extent of metabolite production as a function of time by application of the general model independent approach of deconvolution. The ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015951426191
更新日期：1988-06-01 00:00:00
abstract：PURPOSE:To prepare a thermoreversible gel system able to work as a medium for crystallization at around 20°C, allowing easy retrieval of crystals by simply decreasing the gel temperature. Lactose was selected has model substance for crystallization. METHODS:Water solutions with different% of poloxamer 407, α-Lactose m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0606-3
更新日期：2012-03-01 00:00:00
abstract：:The transepithelial transport of arginine vasopressin (AVP) across cultured rat alveolar epithelial cell monolayers was studied. At 0.1 nM donor [125I]AVP, the radiolabel flux measured in the apical-to-basolateral (AB) direction was about 10 times greater than that in the reverse (BA) direction. HPLC analyses of the b...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018918022865
更新日期：1994-11-01 00:00:00
abstract：PURPOSE:The lack of effective delivery vehicles impedes in vivo applications of siRNA. The trimethyl chitosan-cysteine (TC) nanoparticles (NPs) were developed for in vivo delivery of tumor necrosis factor α (TNF-α) siRNA via oral gavage and intraperitoneal injection. METHODS:The nanoparticles formulated from TC conjug...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1086-4
更新日期：2013-10-01 00:00:00
