Abstract：
PURPOSE:Long-acting injectables (LAIs) are increasingly recognized as an effective therapeutic approach for treating chronic conditions. Many LAIs are formulated to create a poorly soluble depot from which the active agent is delivered over time. This long residing depot can cause localized chronic-active inflammation in the tissue, which has not been well defined in the literature. The purpose of this work is to establish an experimental baseline for describing these responses. METHODS:Non-human primates and rodents were used to examine the response to LAI formulations of two clinically relevant atypical antipsychotics, aripiprazole monohydrate and olanzapine pamoate monohydrate. RESULTS:A foreign body response develops with elevations of key cytokines such as IL-1α, IL-1β, TNFα, and IL6 at the site of injection. However, the tissue response for the two atypical antipsychotics compounds diverge as evidenced by quantitative differences observed in cytokine levels at various time points after dosing. CONCLUSIONS:Our studies show that, while the drugs are in the same therapeutic class, the response to each of these compounds can be distinguished qualitatively and quantitatively, supporting the idea that the injection site reaction involves a multiplicity of factors including the properties of the compound and cellular dynamics at the site of injection.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Paquette SM,Dawit H,Hickey MB,Merisko-Liversidge E,Almarsson O,Deaver DRdoi
10.1007/s11095-014-1308-4subject
Has Abstractpub_date
2014-08-01 00:00:00pages
2065-77issue
8eissn
0724-8741issn
1573-904Xjournal_volume
31pub_type
杂志文章abstract：:Physiologically-based pharmacokinetic (PBPK) models explicitly incorporate tissue-specific blood flows, partition coefficients, and metabolic processes. Since PBPK models are derived using physiologic parameters and interactions of the compound with tissue components, these models are considered to be "bottom up" as o...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-016-2089-8
更新日期：2017-03-01 00:00:00
abstract：PURPOSE:Study the radiolysis of solid-state metoclopramide hydrochloride at various absorbed doses. Elucidate the structure of the degradation products to gain information on the radiolysis mechanisms. METHODS:Solid-state metoclopramide samples were irradiated at several doses with gamma rays and high-energy electrons...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0019-x
更新日期：2006-06-01 00:00:00
abstract：:Interogan variation in tissue distribution of weakly basic drugs such as quinidine, propranolol, and imipramine was investigated as a function of binding to phosphatidylserine (PhS) in tissues. Tissue distributions of these drugs were determined using 10 different tissues at a steady-state plasma concentration and wer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015935031933
更新日期：1990-10-01 00:00:00
abstract：PURPOSE:To describe the pharmacokinetics of SK&F 107647, a synthetic hematoregulatory peptide, in healthy volunteers and in patients with adenocarcinoma. METHODS:SK&F 107647 pharmacokinetics were evaluated in 2 dose-escalation studies. Volunteers received SK&F 107647 as single 15-minute iv infusion doses of 1, 10, 100...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007512617139
更新日期：2000-04-01 00:00:00
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
doi：10.1023/a:1018979419714
更新日期：1994-10-01 00:00:00
abstract：PURPOSE:To investigate the influence of primary crystallization conditions on the mechanical properties and secondary processing behaviour of fluticasone propionate (FP) for carrier based dry powder inhaler (DPI) formulations. METHODS:Young's modulus of FP crystals produced using different anti-solvents was determined...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0640-1
更新日期：2012-04-01 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：:Significant efforts are made to characterize molecular liabilities and degradation of the drug substance (DS) and drug product (DP) during various product life-cycle stages. The in vivo fate of a therapeutic protein is usually only considered in terms of pharmacokinetics (PKs) and pharmacodynamics (PDs). However, the ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-019-2689-1
更新日期：2020-01-03 00:00:00
abstract：PURPOSE:Since the absorption of ceftriaxone (CTO) in the intestine is restricted by its natural physiological characteristics, we developed a series of small synthetic compounds derived from bile acids to promote the absorption of CTO in the gastrointestinal tract. METHODS:Several bile acid derivatives were screened b...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0932-0
更新日期：2013-04-01 00:00:00
abstract：PURPOSE:To evaluate 26 marketed oncology drugs for time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymes. Evaluate TDI-positive drugs for potential to generate reactive intermediates. Assess clinical drug-drug interaction (DDI) risk using static mechanistic models. METHODS:Human liver microsomes and CYP-spe...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0724-6
更新日期：2012-07-01 00:00:00
abstract：PURPOSE:This study was conducted to investigate the cause of incomplete protein release from photopolymerized poly(ethylene glycol) (PEG) hydrogels and verify the protein-protection mechanism provided by iminodiacetic acid (IDA). METHODS:The in vitro release of bovine serum albumin (BSA) from PEG hydrogels prepared un...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-9395-x
更新日期：2006-03-01 00:00:00
abstract：PURPOSE:To measure the charge to mass (Q/M) ratios of the impactor stage masses (ISM) from commercial Flixotide™ 250 μg Evohaler, containing fluticasone propionate (FP), Serevent™ 25 μg Evohaler, containing salmeterol xinafoate (SX), and a combination Seretide™ 250/25 μg (FP/SX) Evohaler metered dose inhalers (MDIs). M...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2544-9
更新日期：2018-11-26 00:00:00
abstract：:A novel application of attenuated total reflectance IR spectroscopy (ATR-IR) was used to monitor the outer several microns of the stratum corneum (SC) and, thereby, demonstrate enhanced percutaneous absorption in vivo in man. 4-Cyanophenol (CP) as a model permeant yielded a unique IR signal, distinct from those of the...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015960815578
更新日期：1990-08-01 00:00:00
abstract：PURPOSE:Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. METHODS:In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tob...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1361-z
更新日期：2014-10-01 00:00:00
abstract：:During protein lyophilization, it is common practice to complete the freezing step as fast as possible in order to avoid protein denaturation, as well as to obtain a final product of uniform quality. We report a contradictory observation made during lyophilization of recombinant tissue-type plasminogen activator (t-PA...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016270103863
更新日期：1995-01-01 00:00:00
abstract：PURPOSE:To determine of the pharmacokinetic profile of methotrexate (MTX) in blood and extracellular fluid (ECF) of VX2 tumor and muscle in rabbits. METHODS:Microdialysis probes were inserted into VX2 tumor and in muscle tissue. Following intravenous administration of MTX (30 mg/kg), serial collection of arterial bloo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011973409022
更新日期：1998-01-01 00:00:00
abstract：PURPOSE:Some patients are unable to generate the peak inspiratory flow rate (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers (DPIs). In this study we tested the hypothesis that the acoustic parameters of an inhalation are related to the PIFR and hence reflect drug delivery. METHODS:A sensitiv...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1371-x
更新日期：2014-10-01 00:00:00
abstract：PURPOSE:Supramolecular Biovectors (SMBV) consist of cross-linked cationic nanoparticles surrounded by a lipid membrane. The purpose was to study the structure of the lipid membrane and to characterise its interaction with the nanoparticles in order to differentiate SMBV from other polymer/lipid associations. METHODS:T...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007504124603
更新日期：2000-07-01 00:00:00
abstract：PURPOSE:Evista (raloxifene HCl) is a nonsteroidal selective estrogen receptor modulator that displays estrogen agonist effects on bone and lipid metabolism but estrogen antagonist effects on the breast and endometrium. The potential for drug-drug interaction between raloxifene and warfarin was assessed in 15 healthy po...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1010904815275
更新日期：2001-07-01 00:00:00
abstract：PURPOSE:Changes in drug absorption and first-pass metabolism have been reported throughout the pediatric age range. Our aim is to characterize both intestinal and hepatic CYP3A-mediated metabolism of midazolam in children in order to predict first-pass and systemic metabolism of CYP3A substrates. METHODS:Pharmacokinet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2458-6
更新日期：2018-07-30 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：:A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a densit...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018921830385
更新日期：1993-09-01 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:For selective inhibition of endothelial cell activation in chronic inflammation, we have developed a dexamethasone-anti-E-selectin immunoconjugate. The present study was performed to evaluate the cellular handling of this immunoconjugate by activated primary endothelial cells and to compare its drug delivery ca...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020769716288
更新日期：2002-11-01 00:00:00
abstract：PURPOSE:For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of ae...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1992-3
更新日期：2016-11-01 00:00:00
abstract：:An empirical mass-transfer model for enteric-coating dissolution that uses in vivo dissolution data to characterize the pH-dependent solubility properties of the polymer film and a mass-transfer coefficient determined from in vivo dissolution or disintegration studies is developed. Once the in vivo mass-transfer coeff...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018986827350
更新日期：1993-02-01 00:00:00
abstract：PURPOSE:To study the structure and function of the intestinal H+/ peptide transporter PET1, we compared its amino acid sequence with those of related transporters belonging to the oligopeptide transporter family PTR, and with more distant transporter families. METHODS:We have developed a new approach to the sequence a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012070726480
更新日期：1997-04-01 00:00:00
abstract：PURPOSE:To study the physical and release properties of different molecular weight (MW) pH- and temperature-responsive statistical terpolymers and beads of N-isopropylacrylamide (NIPAAm), butylmethacrylate (BMA) and acrylic acid (AA). METHODS:Random terpolymers of varying MW were synthesized with NIPAAm/BMA/AA of feed...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018813700535
更新日期：1999-06-01 00:00:00
abstract：:A simple viscometric method was used to quantify mucin-polymer bioadhesive bond strength. Viscosities of 15% (w/v) porcine gastric mucin dispersions in 0.1 N HCl (pH 1) or 0.1 N acetate buffer (pH 5.5) were measured with a Brookfield viscometer in the absence (eta m) or presence (eta t) of selected neutral, anionic, a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015812615635
更新日期：1990-05-01 00:00:00
abstract：PURPOSE:To develop and subsequently evaluate a novel phase inversion-based method used to formulate lipidic nanocapsules. METHODS:Mechanical properties of emulsions prepared by multiinversion phase processes were investigated using a drop tensiometer. Based on the results obtained, a formulation process was developed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016121319668
更新日期：2002-06-01 00:00:00
