Jejunal absorption and metabolism of R/S-verapamil in humans.


PURPOSE:The purpose of this human intestinal perfusion study was to investigate the transport and metabolism of R/S-verapamil in the human jejunum (in vivo). METHODS:A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut perfusion tube in 12 healthy volunteers. Each perfusion lasted for 200 min and was divided into two periods each of 100 min. The inlet concentrations of verapamil were 4.0 and 40 mg/l in period one and two, respectively. RESULTS:The effective jejunal permeability (Peff) of both R- and S-verapamil increased (p < 0.05) when the inlet concentration was increased consistent with saturation of an efflux mechanism. However, both R- and S-verapamil had high intestinal Peff, consistent with complete absorption. The Peff of antipyrine also increased, but there was no difference in the Peff for D-glucose in the two periods. The appearance of R/S-norverapamil in the intestinal perfusate leaving the jejunal segment was non-linear, presumably due to saturation of the CYP3A4 metabolism. CONCLUSIONS:The increased Peff in parallel with increased entering drug concentration is most likely due to saturable efflux by P-glycoprotein(s) in the human intestine.


Pharm Res


Pharmaceutical research


Sandström R,Karlsson A,Knutson L,Lennernäs H




Has Abstract


1998-06-01 00:00:00












  • Swelling and dissolution kinetics during peptide release from erodible anionic gel beads.

    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


    authors: Lee PI

    更新日期:1993-07-01 00:00:00

  • Effects of configuration around the chiral carbon atoms on the crystal properties of ephedrinium and pseudoephedrinium salicylates.

    abstract::The physicochemical properties and crystal structures of the crystalline salts formed by the interaction of an achiral anion, salicylate, with homochiral and racemic ephedrinium and pseudoephedrinium cations were determined. The interaction of ephedrinium or pseudoephedrinium with salicylate in aqueous solution yielde...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Duddu SP,Grant DJ

    更新日期:1994-11-01 00:00:00

  • Crystal growth kinetics of theophylline monohydrate.

    abstract::The crystal growth kinetics of theophylline monohydrate from aqueous buffered supersaturated solutions were investigated at 10, 20, 30, and 40 degrees C. Crystallization experiments were carried out isothermally at pH 6. During growth the crystal count and size distributions were monitored in situ. The growth rate was...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Rodríguez-Hornedo N,Wu HJ

    更新日期:1991-05-01 00:00:00

  • A novel topoisomerase II poison GL331 preferentially induces DNA cleavage at (C/G)T sites and can cause telomere DNA damage.

    abstract:PURPOSE:Topoisomerase II (Topo II) preferentially cuts DNA at alternating purine-pyrimidine repeats. Different Topo II poisons may affect Topo II to produce distinct drug-specific DNA cleavage patterns. GL331 is a new podophyllotoxin derivative exhibiting potent Topo II-poisoning activity. Therefore, the sequence selec...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Lee CC,Huang TS

    更新日期:2001-06-01 00:00:00

  • A Dose Ranging Pharmacokinetic Evaluation of IQP-0528 Released from Intravaginal Rings in Non-Human Primates.

    abstract:PURPOSE:Design of intravaginal rings (IVRs) for delivery of antiretrovirals is often guided by in vitro release under sink conditions, based on the assumption that in vivo release will follow a similar release profile. METHODS:We conducted a dose-ranging study in the female reproductive tract of pigtail macaques using...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Su JT,Teller RS,Srinivasan P,Zhang J,Martin A,Sung S,Smith JM,Kiser PF

    更新日期:2017-10-01 00:00:00

  • pH-Promoted Release of a Novel Anti-Tumour Peptide by "Stealth" Liposomes: Effect of Nanocarriers on the Drug Activity in Cis-Platinum Resistant Cancer Cells.

    abstract:PURPOSE:To evaluate the potential effects of PEGylated pH-sensitive liposomes on the intracellular activity of a new peptide recently characterized as a novel inhibitor of the human thymidylate synthase (hTS) over-expressed in many drug-resistant human cancer cell lines. METHODS:Peptide-loaded pH-sensitive PEGylated (...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Sacchetti F,Marverti G,D'Arca D,Severi L,Maretti E,Iannuccelli V,Pacifico S,Ponterini G,Costi MP,Leo E

    更新日期:2018-09-12 00:00:00

  • Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat.

    abstract:PURPOSE:The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co-administration of the two ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Papathanasiou T,Juul RV,Gabel-Jensen C,Kreilgaard M,Lund TM

    更新日期:2016-11-01 00:00:00

  • Intra- and inter-subject variabilities of CGP 33101 after replicate single oral doses of two 200-mg tablets and 400-mg suspension.

    abstract:PURPOSE:The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subje...

    journal_title:Pharmaceutical research

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Cheung WK,Kianifard F,Wong A,Mathieu J,Cook T,John V,Redalieu E,Chan K

    更新日期:1995-12-01 00:00:00

  • The effects of formulation additives on the degradation of freeze-dried ribonuclease A.

    abstract::The stability of a freeze-dried model protein, ribonuclease A (RNase), was investigated under accelerated storage conditions at 45 degrees C for time periods up to 60 days. Because RNase is a fairly stable molecule around pH 7, lyophilization was performed in phosphate buffers at pH 4.0 or 10.0 to accelerate degradati...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Townsend MW,Byron PR,DeLuca PP

    更新日期:1990-10-01 00:00:00

  • Characterization of Temperature Profiles in Skin and Transdermal Delivery System When Exposed to Temperature Gradients In Vivo and In Vitro.

    abstract:PURPOSE:Performance of a transdermal delivery system (TDS) can be affected by exposure to elevated temperature, which can lead to unintended safety issues. This study investigated TDS and skin temperatures and their relationship in vivo, characterized the effective thermal resistance of skin, and identified the in vitr...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Zhang Q,Murawsky M,LaCount T,Hao J,Kasting GB,Newman B,Ghosh P,Raney SG,Li SK

    更新日期:2017-07-01 00:00:00

  • Transdermal delivery of highly lipophilic drugs: in vitro fluxes of antiestrogens, permeation enhancers, and solvents from liquid formulations.

    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


    authors: Funke AP,Schiller R,Motzkus HW,Günther C,Müller RH,Lipp R

    更新日期:2002-05-01 00:00:00

  • Variations of in vitro nitroglycerine permeation through human epidermis.

    abstract::The fluxes of nitroglycerine (NG) through human abdominal epidermis from different individuals were measured in vitro at 32°C. The mean NG flux for the entire group was 16.9 µg/cm(2) × hr, with a standard deviation of 47.7%. There are no significant differences in the means and the variances of NG fluxes between males...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Langguth P,Spahn H,Mutschler E

    更新日期:1986-02-01 00:00:00

  • The metastatic stage-dependent mucosal expression of sialic acid is a potential marker for targeting colon cancer with cationic polymers.

    abstract:PURPOSE:Locoregional recurrence is the most common complication after adenocarcinoma resection in the colon, despite adjuvant chemotherapy. Therapy efficacy could be improved if designed to target malignant cells by incorporating specific recognition factors in the drugs or the drug vehicles. The aim of this study was ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Azab AK,Kleinstern J,Srebnik M,Rubinstein A

    更新日期:2008-02-01 00:00:00

  • Improved intestinal absorption of an enteric-coated sodium ursodeoxycholate formulation.

    abstract::A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycourso...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Roda A,Roda E,Marchi E,Simoni P,Cerrè C,Pistillo A,Polimeni C

    更新日期:1994-05-01 00:00:00

  • Enhanced accumulation of sialyl Lewis X-carboxymethylpullulan conjugate in acute inflammatory lesion.

    abstract:PURPOSE:E-selectin is a cell adhesion molecule that is specifically expressed in the inflammatory vascular endothelium in response to cytokines such as IL-1 beta and TNF-alpha, and interacts with specific ligands containing sialyl Lewis X (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, SLex). In order to investiga...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Horie K,Sakagami M,Kuramochi K,Hanasaki K,Hamana H,Ito T

    更新日期:1999-02-01 00:00:00

  • In vivo bioequivalence and in vitro similarity factor (f2) for dissolution profile comparisons of extended release formulations: how and when do they match?

    abstract:PURPOSE:To investigate how likely two extended release formulations are to be bioequivalent when they demonstrate f2 similarity. METHOD:Dissolution profiles were simulated using the Weibull model and varying model parameters around those of a reference profile. The f2 values were calculated for the comparisons of each...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Duan JZ,Riviere K,Marroum P

    更新日期:2011-05-01 00:00:00

  • Suppression of cell proliferation by inhibition of estrone-3-sulfate transporter in estrogen-dependent breast cancer cells.

    abstract:PURPOSE:The aim of the study is to suppress the progress of estrogen-dependent breast cancer by inhibiting the membrane transporter, which mediates the internalization of estrone-3-sulfate as estrogen precursor in the cancer cells. METHODS:The uptake of estrone-3-sulfate by estrogen-dependent breast cancer MCF-7 cells...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Nozawa T,Suzuki M,Yabuuchi H,Irokawa M,Tsuji A,Tamai I

    更新日期:2005-10-01 00:00:00

  • Tumor Microenvironment Stimuli-Responsive Polymeric Prodrug Micelles for Improved Cancer Therapy.

    abstract:PURPOSE:The discovery of nano drug delivery system has rendered a great hope for improving cancer therapy. However, there are some inevitable obstacles that constrain its development, such as the physical and biological barriers, the toxicity of carrier materials and the physiological toxicity of drugs. Here, we report...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Zhang Z,Yu M,An T,Yang J,Zou M,Zhai Y,Sun W,Cheng G

    更新日期:2019-12-10 00:00:00

  • A semi-mechanistic gastric emptying model for the population pharmacokinetic analysis of orally administered acetaminophen in critically ill patients.

    abstract:PURPOSE:To develop a semi-mechanistic population pharmacokinetic model based on gastric emptying function for acetaminophen plasma concentration in critically ill patients tolerant and intolerant to enteral nutrition before and after prokinetic therapy. METHODS:Acetaminophen plasma concentrations were available from a...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Ogungbenro K,Vasist L,Maclaren R,Dukes G,Young M,Aarons L

    更新日期:2011-02-01 00:00:00

  • Controlled delivery systems for proteins based on poly(lactic/glycolic acid) microspheres.

    abstract::This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Cohen S,Yoshioka T,Lucarelli M,Hwang LH,Langer R

    更新日期:1991-06-01 00:00:00

  • Pharmaceutical equivalence by design for generic drugs: modified-release products.

    abstract::The Office of Generic Drugs has ensured the high quality of generic products based upon two requirements: pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD). This paradigm has been used with success toward ensuring quality generic drug products that provide the same therapeutic benefit as...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Raw AS,Lionberger R,Yu LX

    更新日期:2011-07-01 00:00:00

  • Salutary effects of two verapamil analogs in traumatic shock.

    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


    authors: Hock CE,Daitch JS,Lefer AM

    更新日期:1985-05-01 00:00:00

  • Mechanistic studies on effervescent-induced permeability enhancement.

    abstract:PURPOSE:To determine the mechanism(s) by which effervescence induces penetration enhancement of a broad range of compounds ranging in size, structure, and other physiocochemical properties across rat and rabbit small intestinal epithelium. METHODS:Effervescent induced penetration enhancement was investigated in vitro ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Eichman JD,Robinson JR

    更新日期:1998-06-01 00:00:00

  • The use of solution theories for predicting water vapor absorption by amorphous pharmaceutical solids: a test of the Flory-Huggins and Vrentas models.

    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


    authors: Hancock BC,Zografi G

    更新日期:1993-09-01 00:00:00

  • Transcellular and lipophilic complex-enhanced intestinal absorption of human growth hormone.

    abstract:PURPOSE:To evaluate the transcellular mechanism of novel enhancers absorption enhancement of human growth hormone (hGH), by examining the involvement of a P-glycoprotein-like efflux system, changes in membrane fluidity, and membrane damage. METHODS:Caco-2 cell monolayers were grown on Snapwell filter supports and plac...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Wu SJ,Robinson JR

    更新日期:1999-08-01 00:00:00

  • Osmotic-driven release kinetics of bioactive therapeutic proteins from a biodegradable elastomer are linear, constant, similar, and adjustable.

    abstract:PURPOSE:The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial gro...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Gu F,Neufeld R,Amsden B

    更新日期:2006-04-01 00:00:00

  • Dependence of dissolution rate on surface area: is a simple linear relationship valid for co-compressed drug mixtures?

    abstract::A quantitative analysis of the dependence of dissolution rate on the relative surface area occupied by two non-interacting drug mixtures from co-compressed slabs is described. The results from the experimental dissolution rates of each component from naproxen/phenytoin co-compressed slabs under laminar flow conditions...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Neervannan S,Southard MZ,Stella VJ

    更新日期:1994-10-01 00:00:00

  • Involvement of indoxyl sulfate in renal and central nervous system toxicities during cisplatin-induced acute renal failure.

    abstract:PURPOSE:The purpose of the present study was to explore the involvement of indoxyl sulfate (IS) in nephrotoxicity and central nervous system (CNS) toxicity in cisplatin (CDDP)-treated rats. MATERIALS AND METHODS:Renal function was evaluated by serum creatinine and BUN levels. The IS levels in the serum, brain and kidn...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Iwata K,Watanabe H,Morisaki T,Matsuzaki T,Ohmura T,Hamada A,Saito H

    更新日期:2007-04-01 00:00:00

  • Antiangiogenic effect of bile acid acylated heparin derivative.

    abstract:PURPOSE:Chemically modified heparin-DOCA was prepared and found to have markedly lower anticoagulant activity than heparin. In the present study, we elucidated the antiangiogenic and antitumoral activities of heparin-DOCA derivative. METHODS:To evaluate the antiangiogenic and antitumoral effects of heparin-DOCA, capil...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Park K,Kim YS,Lee GY,Nam JO,Lee SK,Park RW,Kim SY,Kim IS,Byun Y

    更新日期:2007-01-01 00:00:00

  • Challenging the Relevance of Unbound Tissue-to-Blood Partition Coefficient (Kpuu) on Prediction of Drug-Drug Interactions.

    abstract:PURPOSE:To examine the theoretical/practical utility of the liver-to-blood partition coefficient (Kpuu) for predicting drug-drug interactions (DDIs), and compare the Kpuu-approach to the extended clearance concept AUCR-approach. METHODS:The Kpuu relationship was derived from first principles. Theoretical simulations i...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Sodhi JK,Liu S,Benet LZ

    更新日期:2020-03-25 00:00:00