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 papain to heparin resulting in the highest heparin permeation rate, molar ratios 1:1, 1:2 and 2:1 of papain to heparin were tested. Interactions of heparin with papain were investigated spectro-photometrically. For in vivo studies, 15 mg tablets containing heparin (13%), papain (64%) and hydroxyethylcellulose (22%) were orally administered to rats. RESULTS:Since molar ratio papain to heparin 1:1 resulted in the highest permeation rate, it was used for in vivo studies. The results of binding studies of papain with heparin indicated a strong interaction between papain and heparin. Oral administration of tablets containing LMWH/papain/HEC resulted in sevenfold improvement of plasma anti-Xa activity in comparison to control. For tablets based on heparin/papain/HEC, a relative bioavailability of 9.1% vs. subcutaneous injection was obtained, whereas the relative bioavailability of control was 2.4%. CONCLUSION:The co-administration of papain with heparin represents a new approach in improvement of absorption and bioavailability of orally administered heparin.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Grabovac V,Schmitz T,Föger F,Bernkop-Schnürch Adoi
10.1007/s11095-006-9226-8subject
Has Abstractpub_date
2007-05-01 00:00:00pages
1001-6issue
5eissn
0724-8741issn
1573-904Xjournal_volume
24pub_type
杂志文章abstract：:A method for determination of absorption rate and bioavailability was developed to reduce the influence of intraindividual variability and applied to the absolute intraperitoneal availability of lithium in the rat. In this method the test and the reference doses are given with a few hours' interval, and the resulting ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015939917646
更新日期：1989-09-01 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 objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body. METHODS:The erodible plugs were either prepared by direct compression followed by placing the tablets in...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011940718534
更新日期：1998-03-01 00:00:00
abstract：:Assessment of bioavailability/bioequivalence generally relies on the comparison of rate and extent of drug absorption between products. Rate of absorption is commonly expressed by peak concentration (C(max)) and time to peak concentration (T(max)), although these parameters are indirect measures of absorption rate. Re...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-011-0421-x
更新日期：2011-08-01 00:00:00
abstract：PURPOSE:Tumor vascular normalization by antiangiogenic agents may increase tumor perfusion but reestablish vascular barrier properties in CNS tumors. Vascular priming via nanoparticulate carriers represents a mechanistically distinct alternative. This study investigated mechanisms by which sterically-stabilized liposom...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0823-4
更新日期：2012-12-01 00:00:00
abstract：PURPOSE:A theoretical study was performed to generate a pharmacophore model for chemically diverse structures that specifically interact with the diltiazem binding site of L-type calcium channels. METHODS:Via molecular mechanics and quantum chemical methods solvation energies, logP values, conformational and electroni...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015037800903
更新日期：1999-10-01 00:00:00
abstract：PURPOSE:The heats of reaction between the enantiomers and racemates of ibuprofen and naproxen and human serum albumin (HSA) are to be measured with and without the addition of octanoic acid. The effects of octanoic acid on the free energies of interaction between the drugs and HSA is to be determined and compared to th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016066325476
更新日期：1996-01-01 00:00:00
abstract：:Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0414-9
更新日期：2011-05-01 00:00:00
abstract：PURPOSE:Nasal delivery is a favorable route for vaccination against most respiratory infections, as antigen deposited in the nasal turbinate and Waldeyer's ring areas induce mucosal and systemic immune responses. However, little is known about the nasal distribution of the vaccines, specifically for infants. METHODS:A...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02976-9
更新日期：2021-01-15 00:00:00
abstract：PURPOSE:Good glycaemic control is essential to minimize the risk for diabetes-induced complications. Also, compliance is likely to be higher if the procedure is simple and painless. This study was designed to validate painless intradermal delivery via a patch-like microneedle array. MATERIALS AND METHODS:Diabetes was ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9256-x
更新日期：2007-07-01 00:00:00
abstract：PURPOSE:The aim was to investigate anticancer drug-loaded poly(carbonate-ester) nanospheres as potential drug delivery systems for cancer therapy. METHODS:Functional poly(carbonate-ester) copolymers (HPCP-SD) were synthesized by the incorporation of sulfadiazine as the tumor-targeting groups to hydroxyl groups of poly...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0275-7
更新日期：2010-12-01 00:00:00
abstract：PURPOSE:At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs wit...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2189-0
更新日期：2017-09-01 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：:A new method of analysis for the antihypertensive drug, hydralazine, is introduced. The assay involves the addition of p-nitrobenzaldehyde to blood samples containing hydralazine, to form a stable Schiff's base, hydralazine p-nitrobenzaldehyde hydrazone. The derivative is extracted from the blood into hexane and the s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015915812987
更新日期：1988-06-01 00:00:00
abstract：PURPOSE:To analyze the mechanics of some pharmaceutical agglomerates during uniaxial confined compression by using compression parameters derived from the Heckel, Kawakita and Adams equations, and to study the influence of these compression parameters on the tablet-forming ability of agglomerates. METHODS:Force and di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007575120817
更新日期：2000-08-01 00:00:00
abstract：PURPOSE:To evaluate and classify the hydrolases of the primate lung. METHODS:Homologous series of aromatic, aliphatic, and choline ester substrates were assayed with the pH-stat method to obtain the Michaelis-Menten kinetic constants, Vmax and K(m), for the enzymes in pulmonary alveolar tissue with esterase activity. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012004911942
更新日期：1997-02-01 00:00:00
abstract：:We studied the effects of two verapamil analogs, anipamil and ronipamil, in traumatic shock. Noble-Collip drum trauma produced a shock state characterized by an eight-fold increase in plasma cathepsin D activity, a 13-fold increase in the rate of plasma myocardial depressant factor (MDF) accumulation, and a survival t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016363316777
更新日期：1985-05-01 00:00:00
abstract：PURPOSE:To assess the role of intestinal CYP2D6 in oral first-pass drug clearance by comparing the enzyme content and catalytic activity of a prototype CYP2D6 substrate, metoprolol, between microsomes prepared from human intestinal mucosa and from human livers. METHODS:Microsomes were prepared from a panel of 31 human...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018989211864
更新日期：1999-08-01 00:00:00
abstract：PURPOSE:The pharmacokinetics, analgesic efficacy, and irritancy potential of Buprederm, a new transdermal delivery system of buprenorphine, was evaluated. METHODS:Single and multiple dose pharmacokinetic studies were conducted in mice and rabbits. The analgesic efficacy and skin irritation potential were determined by...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9470-6
更新日期：2008-05-01 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：:Leucine enkephalin (YGGFL) undergoes rapid degradation in sheep nasal mucosa to yield GGFL which is further degraded to FL. The activity of the nasal mucosal homogenate against YGGFL and GGFL (t1/2 12 and 7 min) was significantly greater than that observed with a nasal wash fluid (t1/2 40 and 13 min). The effect of cy...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018946829225
更新日期：1994-12-01 00:00:00
abstract：PURPOSE:This study was conducted to demonstrate the use of differential scanning calorimetry (DSC) in detecting and measuring beta-relaxation processes in amorphous pharmaceutical systems. METHODS:DSC was employed to study amorphous samples of poly(vinylpyrrolidone) (PVP), indomethacin (IM), and ursodeoxycholic acid (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-9044-4
更新日期：2006-02-01 00:00:00
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...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015866714224
更新日期：1992-08-01 00:00:00
abstract：PURPOSE:Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications. METHODS:Nanofibr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2428-z
更新日期：2018-05-22 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：: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:With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. METHODS:Mono- and multi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020354809581
更新日期：2002-09-01 00:00:00
abstract：PURPOSE:To study the relative thermodynamic and kinetic stabilities of neotame anhydrate polymorphs A, D, F, and G, and to develop a quantitative method for analyzing polymorphic mixtures of A and G by powder X-ray diffractometry (PXRD). METHODS:Based on the melting points, heats of fusion, and densities of the four p...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020334305038
更新日期：2002-09-01 00:00:00
abstract：PURPOSE:Because interleukin-10 (IL-10) seems a promising new antifibrotic drug, we investigated the pharmacokinetic and biodistribution profile of this potent therapeutic cytokine in rats with extensive liver fibrosis (BDL-3). IL-10 receptor expression was also determined in relation to these aspects. METHODS:To study...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000048199.94510.b0
更新日期：2004-11-01 00:00:00
abstract：PURPOSE:The objective of this study was to investigate the possible influence of probenecid on morphine transport across the blood-brain barrier (BBB) in rats. METHODS:Microdialysis probes, calibrated using retrodialysis by drug, were placed into the striatum and jugular vein of seven Sprague-Dawley rats. Morphine was...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023250900462
更新日期：2003-04-01 00:00:00
