M E Brewster

Janssen Research & Development, LLC, Raritan, New Jersey, United States

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Publications (244)692.26 Total impact

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    ABSTRACT: We hypothesized that nanosuspensions could be promising for the delivery of the poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327. Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for parenteral and oral administrations and (ii) to compare this nanosuspension with other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics. Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based nanoparticles, (ii) self-assembling PEG750-p-(CL-co-TMC) polymeric micelles, (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.5). All the nano-formulations presented a size below 200 nm. Injections of the highest possible dose of the three nano-formulations did not induce any side effects in mice. In contrast, the maximum tolerated dose of the control Captisol solution was 20-fold lower than its highest possible dose. The highest regrowth delay of A-431-tumor-bearing nude mice was obtained with MTKi-327 nanosuspension, administered intravenously, at a dose of 650 mg/kg. After intravenous and oral administration, the AUC0-∞ of MTKi-327 nanosuspension was 2.4-fold greater than that of the Captisol solution. Nanosuspension may be considered as an effective anti-cancer MTKi-327 delivery method due to (i) the higher MTKi-327 maximum tolerated dose, (ii) the possible intravenous injection of MTKi-327, (iii) its ability to enhance the administered dose and (iv) its higher efficacy.
    European Journal of Pharmaceutics and Biopharmaceutics. 05/2014;
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    ABSTRACT: This review summarizes the current knowledge on anatomy and physiology of the human gastrointestinal tract in comparison with that of common laboratory animals (dog, pig, rat and mouse) with emphasis on in vivo methods for testing and prediction of oral dosage form performance. A wide range of factors and methods are considered in addition, such as imaging methods, perfusion models, models for predicting segmental/regional absorption, in vitro in vivo correlations as well as models to investigate the effects of excipients and the role of food on drug absorption. One goal of the authors was to clearly identify the gaps in todays knowledge in order to stimulate further work on refining the existing in vivo models and demonstrate their usefulness in drug formulation and product performance testing.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 03/2014; · 2.61 Impact Factor
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    ABSTRACT: Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silico and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will when successful provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 11/2013; · 2.61 Impact Factor
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    ABSTRACT: OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organisation, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery and. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using API, formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and) and modified-release formulations, as well as allowing optimisation of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo is expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 11/2013; · 2.61 Impact Factor
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    ABSTRACT: Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has often been ignored. More recently, the switch to assessing drug products in a more biorelevant and mechanistic manner has advanced the understanding of drug formulation behavior. Notwithstanding this evolution, predicting the in vivo biopharmaceutical performance of formulations that rely on complex intraluminal processes (e.g. solubilization, supersaturation, precipitation…) remains extremely challenging. Concomitantly, the increasing demand for complex formulations to overcome low drug solubility or to control drug release rates urges the development of new in vitro tools. Development and optimizing innovative, predictive Oral Biopharmaceutical Tools is the main target of the OrBiTo project within the Innovative Medicines Initiative (IMI) framework. A combination of physico-chemical measurements, in vitro tests, in vivo methods, and physiology-based pharmacokinetic modeling is expected to create a unique knowledge platform, enabling the bottlenecks in drug development to be removed and the whole process of drug development to become more efficient. As part of the basis for the OrBiTo project, this review summarizes the current status of predictive in vitro assessment tools for formulation behaviour. Both pharmacopoeia-listed apparatus and more advanced tools are discussed. Special attention is paid to major issues limiting the predictive power of traditional tools, including the simulation of dynamic changes in gastrointestinal conditions, the adequate reproduction of gastrointestinal motility, the simulation of supersaturation and precipitation, and the implementation of the solubility-permeability interplay. It is anticipated that the innovative in vitro biopharmaceutical tools arising from the OrBiTo project will lead to improved predictions for in vivo behavior of drug formulations in the GI tract.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 08/2013; · 2.61 Impact Factor
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    ABSTRACT: Supersaturating Drug Delivery Systems (SDDS) hold the promise of enabling intestinal absorption for difficult-to-formulate, poorly soluble drug candidates based on a design approach that includes (1) converting the drug into a high energy or rapidly dissolving system which presents a supersaturated solution to the gastrointestinal environment and (2) dosage form components that act to stabilize the formed metastable drug solution through nucleation and/or crystal growth inhibition. The appropriate development and study of SDDS require that useful and biorelevant supersaturation and precipitation assays are available. This review summarizes different methodological aspects of currently available in vitro assays, including the generation of supersaturation (solvent shift, pH shift or formulation-induced), the quantification of supersaturation and the detection of precipitation. Also down-scaled approaches, including 96-well plate setups, are described and situated in the pharmaceutical development cycle based on their consumption of API as well as time requirements. Subsequently, the ability to extrapolate in vitro supersaturation assessment to the in vivo situation is discussed as are direct and indirect clinical tools that can shed light on SDDS. By emphasizing multiple variables that affect the predictive power of in vitro assays (e.g. the nature of the test media, hydrodynamics, temperature and sink versus non-sink conditions), this review finally highlights the need for further harmonization and biorelevance improvement of currently available in vitro procedures for supersaturation and precipitation evaluation.
    International Journal of Pharmaceutics 11/2012; · 3.99 Impact Factor
  • Journal of Pharmaceutical Sciences 05/2012; 101(9):2989-95. · 3.13 Impact Factor
  • Source
    The XVI International Cyclodextrin Symposium, Tianjin, China; 05/2012
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    ABSTRACT: Methotrexate (MTX) has been used to treat rheumatoid arthritis at low doses and leukemia at high doses; however, this drug can produce severe side effects. Our hypothesis is that MTX side effects can be attenuated by directing the drug to the target cells (i.e., leukocytes) using (cyclo(1,12)PenPRGGSVLVTGC) peptide (cIBR). To test this hypothesis, MTX was conjugated to the N‐terminus of cIBR peptide to give MTX–cIBR conjugate. MTX–cIBR (5.0 mg/kg) suppressed joint arthritis in adjuvant arthritis rats and prevented periarticular inflammation and bone resorption of the limb joints. In vitro, the toxicity of MTX–cIBR peptide against Molt‐3 T cells was inhibited by anti‐lymphocyte function‐associated antigen‐1 (LFA‐1) antibody and cIBR peptide in a concentration‐dependent manner, suggesting that the uptake of MTX–cIBR was partially mediated by LFA‐1. Chemical stability studies indicated that MTX–cIBR was most stable at pH 6.0. The MTX portion of MTX–cIBR was unstable under acidic conditions, whereas the cIBR portion was unstable under basic conditions. In biological media, MTX–cIBR had short half lives in rat plasma (44 min) and homogenized rat heart tissue (38 min). This low plasma stability may contribute to the low in vivo efficacy of MTX–cIBR; therefore, there is a need to design a more stable conjugate to improve the in vivo efficacy. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3275–3291, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: The investigational synthetic ozonide, OZ209, has previously been shown to have high binding affinity for sulfobutylether7–β‐cyclodextrin [(SBE)7–β‐CD] resulting in altered pharmacokinetics when administered intravenously to rats in a (SBE)7–β‐CD aqueous formulation. In the present study, OZ209 and (SBE)7–β‐CD have been used to probe whether a modified β‐CD excipient, on systemic administration, can bind to and alter the pharmacokinetics of a coadministered drug. When (SBE)7–β‐CD was administered 60 min after OZ209, a spike in the concentration of OZ209 in blood and plasma was detected within 2 min of the (SBE)7–β‐CD infusion, and this was accompanied by a temporary decrease in the whole blood‐to‐plasma partitioning ratio of OZ209, the duration of which was dependent upon the dose of (SBE)7–β‐CD. Administration of (SBE)7–β‐CD also resulted in increased urinary excretion of OZ209. By contrast, administration of (SBE)7–β‐CD 4 h prior to OZ209 had no pronounced effect on the blood or plasma pharmacokinetics of OZ209, consistent with the (SBE)7–β‐CD having been largely eliminated prior to the administration of OZ209. This study is the first to demonstrate an in vivo drug–excipient interaction between a modified β‐CD and a coadministered drug, and also demonstrates that such an interaction can be avoided through appropriate consideration of CD pharmacokinetics. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3381–3389, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: Human serum albumin is the most abundant protein in the blood. It is clinically used in the treatment of severe hypoalbuminemia and as a plasma expander. The use of albumins as a carrier for drugs is currently being developed, and some are now in the preclinical and clinical trial stages. The main technologies for utilizing an albumin as a drug carrier are protein fusion, polymerization and surface modification, and so on. Among these technologies, albumin dimerization has wide clinical applications as a plasma expander as well as a drug carrier. Despite the fact that many reports have appeared on drugs using an albumin dimer as a carrier, our knowledge of the characteristics of the albumin dimer itself is incomplete. In this review, we summarize the structural characteristics of recombinant albumin dimers produced by two methods, namely, chemical linkage with 1,6‐bis(maleimido)hexane and genetically linked with an amino acid linker, and the physicochemical characteristics and biological properties of these preparations. Finally, the potential for pharmaceutical applications of albumin dimers in clinical situations is discussed. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3033–3046, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: We examined the effect of acylcarnitines on the in situ bioavailability of lucifer yellow (LY) from the loops of small and large intestines of rats. The area under the blood concentration of LY versus time curve (AUC) from the jejunum was significantly increased by the treatments of the loop with 100 µM lauroylcarnitine (LC) or 100 µM palmitoylcarnitine (PC) (fourfold and 17‐fold, respectively). No marked change in the expression of claudin‐4 protein was observed by the treatments. On the contrary, the expression of P‐glycoprotein (P‐gp) was decreased by the treatment, more greatly by PC than by LC, suggesting that increases in the bioavailability of LY by LC and PC are associated with the decreased expression of P‐gp in jejunum. The increase in the bioavailability was also observed for colon by the treatment of LC, but not that of PC. LC decreased the expression of claudin‐4 protein, whereas PC decreased the expression of P‐gp in colon. Therefore, LC and PC appear to have different impact on the intestinal transporters depending on the site (i.e., jejunum and colon). © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3511–3517, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: Many boronic acid‐containing molecules are currently under investigation as possible therapeutics. An increase in the knowledge of the physical and chemical properties of these compounds will lead to their improved formulation into usable dosage forms. The current study describes the formation and characterization of a boronic acid anhydride, called a boroxine. The model boronic acid, 4‐methoxybenzeneboronic acid is used. The current study demonstrates the utility of thermal (differential scanning calorimetry and thermogravimetric analysis) and spectral (solid‐state nuclear magnetic resonance and ultraviolet spectroscopy) methods to quantitate and characterize the boronic acid and its boroxine, validated against definitive structures solved by single‐crystal X‐ray diffraction. The present work also demonstrates that the hydrolysis of the boroxine in the presence of water is very rapid in a time scale relative to drug substance manufacture and product formulation. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3190–3198, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: Amorphous solid dispersions have great potential for enhancing oral absorption of poorly soluble drugs. Crystallization behavior during storage and after exposure to aqueous media must be examined in detail for designing stable and effective amorphous formulations, and it is significantly affected by the intrinsic properties of an amorphous drug. Many attempts have been made to correlate various thermodynamic parameters of pharmaceutical glasses with their crystallization behavior; however, variations in model drugs that could be used for such investigation has been limited because the amorphous characteristics of drugs possessing a high crystallization tendency are difficult to evaluate. In this study, high‐speed differential scanning calorimetry, which could inhibit their crystallization using high cooling rates up to 2000°C/s, was employed for assessing such drugs. The thermodynamic parameters of the glasses, including glass transition temperature (T g) and fragility, were obtained to show that their crystallization tendency cannot be explained simply by the parameters, although there have been general thought that fragility may be correlated with crystallization tendency. Also investigated was correlation between the thermodynamic parameters and crystallization tendency upon contact with water, which influences in vivo efficacy of amorphous formulations. T g was correlated well with the crystallization tendency upon contact with water. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3239–3248, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: The purpose of this work was to study the permeability of two relatively lipophilic sulfenamide prodrugs of linezolid (clogP 0.85), N‐(phenylthio)linezolid (1, clogP 2.77) and N‐[(2‐ethoxycarbonyl)ethylthio]linezolid (2, clogP 1.43), across Caco‐2 cell monolayers. Both prodrugs were found to convert to linezolid in the donor compartment presumably from the reaction with free thiol groups on proteins on the surface of the Caco‐2 cells, as no conversion was seen in the donor compartment media per se. Neither of the prodrugs could be detected in the receptor phase from either apical (AP) to basolateral (BL) or BL to AP studies. However, the appearance of linezolid in the receptor phase was biphasic with an initial rapid phase suggesting that the prodrugs were indeed more permeable, and for a short period, some prodrug was able to permeate in competition with conversion to linezolid on the donor phase surface. It appears that the prodrug was able to permeate was rapidly converted to linezolid prior to acceptor phase appearance. The second slower phase was due to the permeability of the donor‐phase‐formed linezolid, with the slopes similar to those from control experiments with linezolid. The limitations and possible utility of oral sulfenamide prodrugs are discussed. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3134–3141, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: Levofloxacin is a broad‐spectrum antibiotic that exists as a hemihydrate under ambient conditions. In addition to the hemihydrate, there are three known crystalline anhydrate forms, denoted as α, β, and γ. In this study, differential scanning calorimetry (DSC), thermogravimetric analysis, Raman spectroscopy, single‐crystal and powder X‐ray diffraction, and solid‐state NMR spectroscopy were used to investigate the transitions that occurred upon dehydration to the anhydrate as well as additional transitions that occurred to the anhydrous material upon heating/cooling. An enantiotropic conversion was observed in the DSC around 54°C corresponding to the conversion of the γ form to a new form, denoted as the δ form. Raman spectroscopy, powder X‐ray diffraction, and solid‐state NMR spectroscopy confirmed that a new crystalline form was being produced. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3319–3330, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: The objective of this study is to evaluate the ability of C60/2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CyD) naonparticles to generate reactive oxygen species (ROS) and to induce cell toxicity by the photoirradiation. C60 nanoparticles were prepared by cogrinding with HP‐β‐CyD for 3 h at 4°C under reduced pressure. The photodynamic activity of C60/HP‐β‐CyD nanoparticles was evaluated by spectroscopic methods, including the electron spin resonance spin‐trapping method, and by the cell viability test using Hela cells. C60/HP‐β‐CyD nanoparticles efficiently generated not only superoxide anion radical (O2·−) and hydroxyl radical (·OH), but also singlet oxygen (1O2) through photoirradiation. The ROS generation was enhanced by decreasing the mean particle diameter of C60 nanoparticles, and the particle size smaller than 90 nm showed a high generation of ·OH and 1O2. In addition, HP‐β‐CyD enhanced the generation of 1O2, compared with polyvinylpyrrolidone (an effective solubillizer for C60), due to partial disposition of C60 in the hydrophobic CyD cavity. Furthermore, C60/HP‐β‐CyD nanoparticles showed cell toxicity after the light irradiation, but no toxicity was observed without the light irradiation. Therefore, HP‐β‐CyD is useful for the preparation of stable C60 nanoparticles with high ROS generation ability, and C60/HP‐β‐CyD nanoparticles are a promising photosensitizer for photodynamic therapy. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3390–3397, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: The biopharmaceutical and physicochemical properties of two new cyclic prodrugs (CA‐[cychexalanine (Cha4), d‐Leu5]‐Enkephalin (Enk) and coumarinic acid (CA)‐[Cha4, d‐Ala5]‐Enk) of opioid peptides that were designed to be stable to oxidative metabolism by cytrochrome P‐450 enzymes in the intestinal mucosa are described in this paper. Two‐dimensional nuclear magnetic resonance studies and molecular dynamics simulations showed that these cyclic prodrugs exhibit unique solution conformations (i.e., type I β‐turns), which are favorable for transcellular permeation. The calculated molecular surface areas and cLog P values confirmed that these new cyclic prodrugs are more lipophilic than linear opioid peptides and, thus, they should exhibit better transcellular permeation characteristics. However, Caco‐2 cell permeation studies showed that the cyclic prodrugs were substrates for apically polarized efflux transporters (e.g., P‐glycoprotein, which significantly limited their transcellular permeation). Permeability studies using an in situ rat intestinal perfusion model confirmed the poor intestinal permeation characteristics of CA‐[Cha4, d‐Leu5]‐Enk and CA‐[Cha4, d‐Ala5]‐Enk as well as the stability of these two new cyclic prodrugs of opioid peptides to oxidative metabolism. In conclusion, these data clearly show that oral absorption of cyclic prodrugs of opioid peptides can only be achieved by designing molecules devoid of substrate activity for both cytrochrome P‐450 enzymes and efflux transporters in the intestinal mucosa. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3500–3510, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: AbstractUDP‐glucuronosyltransferase 1A10 (UGT1A10) catalyzes glucuronidation of a wide range of chemicals including many drugs. Here, we report the first in silico model quantifying the substrate selectivity and binding affinity (as K m) for UGT1A10. The training set for model construction comprises 32 structurally diverse compounds, which are known substrates for UGT1A10. The model was derived by applying the standard VolSurf method involving calculation of VolSurf descriptors and partial least square (PLS) analyses. The yielded PLS model with two components shows statistical significance in both fitting and internal predicting (r 2 = 0.827, q 2 = 0.774). The model predictability was further validated against a test set of 11 external compounds. The activity values for all test substrates were predicted within 1 log unit. Moreover, the model reveals an overlay of chemical features influencing the enzyme–substrate binding. Those include the size and shape, capacity factors, hydrophilic regions, hydrophobic regions, and polarizability. In conclusion, the VolSurf approach is successfully utilized to establish a predictive model for UGT1A10. The derived model should be an efficient tool for high‐throughput prediction of UGT1A10 metabolism. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3531–3539, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor
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    ABSTRACT: The clearance (Cl) and volume of distribution (V ss) of a lipophilic, lymphatically transported drug, halofantrine (Hf) have been evaluated after intravenous delivery to the systemic circulation in ex vivo lymph and plasma, and compared with the data obtained after administration of a lipid‐based emulsion and a lipid‐free cosolvent formulation. Systemic Cl and V ss were significantly lower (approximately twofold) after delivery of Hf in lymph or the emulsion when compared with the administration in plasma or the cosolvent formulation. Preadministration of drug‐free lymph, immediately before administration of drug in plasma, however, resulted in plasma profiles consistent with that obtained after administration of drug in lymph/emulsion. Where drug and lipid entered the systemic circulation coincidentally, systemic Cl of Hf, therefore, appeared to be relatively unaffected by the route of entry to the systemic circulation (i.e. via the lymph or the blood), but more significantly altered by total plasma lipid levels. Because temporal changes to plasma lipid levels occur as a result of the absorption of formulation or food‐derived lipids and the infusion of intravenous lipid emulsions, the current data suggest that a mismatch in plasma lipid levels after intravenous and oral administrations may lead to differences in drug Cl and errors in bioavailability assessment. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3540–3546, 2012
    Journal of Pharmaceutical Sciences 01/2012; 101(9). · 3.13 Impact Factor

Publication Stats

4k Citations
692.26 Total Impact Points


  • 2014
    • Janssen Research & Development, LLC
      Raritan, New Jersey, United States
  • 2013
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany
  • 1995–2012
    • University of Iceland
      • Faculty of Pharmaceutical Sciences
      Reykjavík, Capital Region, Iceland
    • Albert Einstein College of Medicine
      New York City, New York, United States
  • 2003–2011
    • KU Leuven
      • Laboratory for Pharmacotechnology and Biopharmacy
      Leuven, VLG, Belgium
  • 2004–2010
    • Catholic University of Louvain
      • Institute of Experimental and Clinical Research (IREC)
      Walloon Region, Belgium
  • 2002–2010
    • Johnson & Johnson
      New Brunswick, New Jersey, United States
  • 1982–2009
    • University of Florida
      • • College of Pharmacy
      • • Department of Physiological Sciences
      • • Department of Medicinal Chemistry
      Gainesville, FL, United States
  • 2008
    • Maastricht University
      • Genetica en Celbiologie
      Maastricht, Provincie Limburg, Netherlands
  • 2006–2007
    • The Ohio State University
      • William G. Lowrie Department of Chemical and Biomolecular Engineering
      Columbus, OH, United States
  • 2005
    • California Institute of Technology
      • Division of Chemistry and Chemical Engineering
      Pasadena, CA, United States
  • 1997
    • Hebrew University of Jerusalem
      Yerushalayim, Jerusalem District, Israel
    • Weizmann Institute of Science
      • Department of Biological Regulation
      Tel Aviv, Tel Aviv, Israel