journal
MENU ▼
Read by QxMD icon Read
search

Biopharmaceutics & Drug Disposition

journal
https://www.readbyqxmd.com/read/28214380/application-of-the-mechpeff-model-to-predict-passive-effective-intestinal-permeability-in-the-different-regions-of-the-rodent-small-intestine-and-colon
#1
D Pade, M Jamei, A Rostami-Hodjegan, D B Turner
A major component of Physiologically-Based Pharmacokinetic (PBPK) models is prediction of the rate and extent of absorption of orally dosed drugs for which knowledge of effective passive intestinal permeability (Peff ) is essential. Single pass intestinal perfusion (SPIP) studies are used to establish effective permeability in vivo but are difficult to perform in rodents while mechanistic models to predict drug Peff in rat and mouse have not been published. This work evaluates the predictive performance of the 'MechPeff' model to predict Peff in the rodent intestine based upon knowledge of regional gut physiology and drug-specific physicochemical parameters...
February 18, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28207929/optimisation-of-intestinal-microsomal-preparation-in-the-rat-a-systematic-approach-to-assess-the-influence-of-various-methodologies-on-metabolic-activity-and-scaling-factors
#2
Oliver J D Hatley, Christopher R Jones, Aleksandra Galetin, Amin Rostami-Hodjegan
The metabolic capacity of the intestine and its importance as the initial barrier to systemic exposure can lead to under-estimation of first-pass, and thus overestimation of oral bioavailability. However, the in vitro tools informing estimates of in vivo intestinal metabolism are limited by the complexity of the in vitro matrix preparation and uncertainty with the scaling factors for in vitro to in vivo extrapolation. A number of methods currently exist in the literature for the preparation of intestinal microsomes; however, the impact of key steps in the preparation procedure has not been critically assessed...
February 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28207160/pharmacokinetic-interactions-in-mice-between-irinotecan-and-mbl-ii-141-an-abcg2-inhibitor
#3
Emilie Hénin, Mylène Honorat, Jérôme Guitton, Attilio Di Pietro, Léa Payen, Michel Tod
PURPOSE: The chromone derivative MBL-II-141, specifically designed to inhibit ABCG2, was previously demonstrated to combine strong inhibition potency, low toxicity and good efficiency in reversing resistance to irinotecan in a xenografted mouse model. Here, the pharmacokinetic interactions in mice between irinotecan, its active metabolite SN-38 and MBL-II-141 were characterized quantitatively in the blood and in the brain. METHODS: Compartmental models were used to fit the data...
February 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28152562/a-comparative-evaluation-of-models-to-predict-human-intestinal-metabolism-from-nonclinical-data
#4
Estelle Yau, Carl Petersson, Hugues Dolgos, Sheila Annie Peters
Extensive gut metabolism is often associated with the risk of low and variable bioavailability. Prediction of the fraction of drug escaping gut wall metabolism as well as transporter-mediated secretion (Fg ) has been challenged by the lack of appropriate preclinical models. The purpose of this study is to compare the performance of models that are widely employed in the pharmaceutical industry today to estimate Fg , and based on the outcome to provide recommendations for the prediction of human Fg during drug discovery and early drug development...
February 2, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28144964/pharmacokinetics-and-protein-binding-of-mpt0b292
#5
Yu-En Tien, Chan-Jung Li, Jing-Ping Liou, Jang-Yang Chang, Jin-Ding Huang
MPT0B292 was identified through screening of compounds able to selectively acetylate α-tubulins in cells and exhibited potent anti-tumor, anti-angiogenesis and anti-metastatic effects in vitro and in vivo. Because of poor water solubility, MPT0B292 is difficult to formulate with conventional approaches and hence difficulties are experienced in research practices. We mixed MPT0B292 with albumin in the aqueous solvent to form drug albumin nanoparticles with the size range around 333 nm. We investigated unbound fractions of these nanoparticles in different or same albumin concentration solutions...
February 1, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28102538/comparing-early-liver-graft-function-from-heart-beating-and-living-donors-a-pilot-study-aiming-to-identify-new-biomarkers-of-liver-injury
#6
Qi Joy Yang, Michael Kluger, Krzysztof Goryński, Janusz Pawliszyn, Barbara Bojko, Ai-Ming Yu, Keumhan Noh, Markus Selzner, Angela Jerath, Stuart McCluskey, K Sandy Pang, Marcin Wąsowicz
: Liver and kidney functions among recipients of liver transplantation (LT) surgery with heart beating (HBD, n = 13) or living donors (LD, n = 9) with different cold ischemic times were examined during the neohepatic phase for clearing rocuronium bromide (ROC, cleared by liver and kidney) and tranexamic acid (TXA, cleared by kidney). Solid phase micro-extraction and LC-MS/MS was applied to determine the plasma concentrations of ROC and TXA, and creatinine was determined by standard laboratory methods...
January 19, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28099756/levofloxacin-effect-on-erlotinib-absorption-evaluation-of-the-interaction-in-undernutrition-situations-through-population-pharmacokinetic-analysis-in-rats
#7
Alejandro Pérez Pitarch, Beatriz Guglieri-López, Amparo Nacher, Virginia Merino, Matilde Merino-Sanjuan
The main objective of this study was to develop a pharmacokinetic model in order to describe the intestinal absorption of erlotinib in rat and to quantify the interaction of levofloxacin on this process in well- and undernourished rats. Absorption studies were performed in male Wistar rats. Concentration-time profiles in proximal and distal intestine were analysed through non-linear mixed effect modelling using the NONMEM software version 7.3. Simulations were performed in order to explore the influence of covariates on apparent absorption rate constant...
January 18, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28092695/absorption-distribution-and-excretion-of-the-anti-tuberculosis-drug-delamanid-in-rats-extensive-tissue-distribution-suggests-potential-therapeutic-value-for-extrapulmonary-tuberculosis
#8
Masakazu Shibata, Yoshihiko Shimokawa, Katsunori Sasahara, Noriaki Yoda, Hiroyuki Sasabe, Mitsunari Suzuki, Ken Umehara
Delamanid (OPC-67683, Deltyba(TM) , nitro-dihydro-imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug-resistant tuberculosis. The absorption, distribution, and excretion of delamanid-derived radioactivity were investigated after a single oral administration of (14) C-delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 hours postdose, and thereafter decreased slowly. Radioactivity levels were 3- to 5-fold higher in lung tissue at time to maximum concentration compared with plasma...
January 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28084034/prediction-of-liver-volume-a-population-based-approach-to-meta-analysis-of-pediatric-adult-and-geriatric-populations-an-update
#9
Ben G Small, Bernd Wendt, Masoud Jamei, Trevor N Johnson
: Liver volume is a critical scaling factor for predicting drug clearance in physiologically-based pharmacokinetic modeling and for both donor/recipient graft size estimation in liver transplantation. Accurate and precise estimation of liver volume is therefore essential. The objective here was to extend an existing meta-analysis using a non-linear mixed effects modeling approach for the estimation of liver volume to other race groups and pediatric and geriatric populations. Interrogation of the PubMed® database was undertaken using a text string query to ensure an objective retrieval of liver volume data for the modeling exercise as possible...
January 13, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28039878/quantifying-gut-wall-metabolism-methodology-matters
#10
Oliver J D Hatley, Christopher R Jones, Aleksandra Galetin, Amin Rostami-Hodjegan
Oral administration continues to be the dominant route for dosing of small molecules. Therefore having adequate oral bioavailability remains a key component for the success of drug candidates. Amongst various factors determining the overall bioavailability, the role of the intestinal metabolism is commonly overlooked [1]. Intestinal microsomes are commercially available, analogous to hepatic microsomes which are an essential part of the early drug discovery DMPK (Drug Metabolism and Pharmacokinetics) assessment...
December 30, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28032362/prioritizing-pharmacokinetic-drug-interaction-precipitants-in-natural-products-application-to-oatp-inhibitors-in-grapefruit-juice
#11
Emily J Johnson, Christina S Won, Kathleen Köeck, Mary F Paine
Natural products, including botanical dietary supplements and exotic drinks, represent an ever-increasing share of the health care market. The parallel ever-increasing popularity of self-medicating with natural products increases the likelihood of co-consumption with conventional drugs, raising concerns for unwanted natural product-drug interactions. Assessing the drug interaction liability of natural products is challenging due to the complex and variable chemical composition inherent to these products, necessitating a streamlined preclinical testing approach to prioritize precipitant individual constituents for further investigation...
December 29, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28027412/inhibitory-effect-of-ezetimibe-can-be-prevented-by-an-administration-interval-of-4%C3%A2-h-between-%C3%AE-tocopherol-and-ezetimibe
#12
Shunsuke Nashimoto, Yuki Sato, Yoh Takekuma, Mitsuru Sugawara
Tocopherol is used not only as an ethical drug but also as a supplement. In 2008, Narushima et al. reported that α-tocopherol is partly transported via an intestinal cholesterol transporter, Niemann-Pick C1-Like 1 (NPC1L1). Ezetimibe, a selective inhibitor of NPC1L1, is administered for a long time to inhibit cholesterol absorption and there is a possibility that absorption of α-tocopherol is also inhibited by ezetimibe. In this study, we investigated the influence of ezetimibe on the absorption of α-tocopherol with single administration and long-term administration...
December 27, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28027398/physiologically-based-pharmacokinetic-predictions-of-intestinal-bcrp-mediated-effect-of-telmisartan-on-the-pharmacokinetics-of-rosuvastatin-in-humans
#13
Soo Hyeon Bae, Wan-Su Park, Seunghoon Han, Gab-Jin Park, Jongtae Lee, Taegon Hong, Sangil Jeon, Dong-Seok Yim
It was recently reported that the Cmax and AUC of rosuvastatin increases when it is coadministered with telmisartan. The aim of this study was to explore the mechanism of the interaction of telmisartan and rosuvastatin. A full-PBPK model of telmisartan was developed, and the rosuvastatin model in Simcyp (version 15)'s drug library was modified to reflect ethnic differences in rosuvastatin exposure. PK characteristics, including intestinal and hepatic transporter / enzyme specificities of telmisartan and rosuvastatin, were incorporated into the PBPK models to simulate a rosuvastatin (20 mg) - telmisartan (80 mg) multiple dose drug interaction study...
December 27, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28004396/the-absorption-kinetics-of-ketoconazole-plays-a-major-role-in-explaining-the-reported-variability-in-the-level-of-interaction-with-midazolam-exploring-the-interplay-between-formulation-and-inhibition-of-gut-wall-and-liver-metabolism-by-using-different-doses
#14
Bo Liu, H Kim Crewe, Mahmut Ozdemir, Karen Rowland Yeo, Geoffrey Tucker, Amin Rostami-Hodjegan
The impact of different single oral doses of ketoconazole (KTZ) (100, 200 and 400 mg) and of staggering its dosage (400 mg at -12, -2, 0, 2 and 4 h), with respect to the administration of a single 5 mg oral dose of midazolam (MDZ) on the extent of inhibition of the metabolism of the latter, was evaluated in healthy subjects in two separate studies. Escalation of KTZ dosage resulted in 2.3- (1.9), 2.7- (1.7) and 4.2- (2.5) fold increases in the mean AUC(0,12 h) (and Cmax ) values of MDZ. Dose-staggering was associated with 3...
December 21, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27977852/unequivocal-evidence-supporting-the-segregated-flow-intestinal-model-that-discriminates-intestine-versus-liver-first-pass-removal-in-pbpk-modeling
#15
K Sandy Pang, Qi Joy Yang, Keumhan Noh
Merits of the segregated flow model (SFM), highlighting the intestine as an inert serosa and active enterocyte c regions, with a smaller fractional (fQ  < 0.3) intestinal flow (QI ) perfusing the enterocyte region, were described. Less drug in the circulation reaches the enterocytes due to the lower flow (fQ QI ) in comparison to drug absorbed from the gut lumen, fostering the idea of route-dependent intestinal removal. The SFM was superior over the traditional model (TM), which views the serosa and enterocytes as a well-mixed tissue perfused by 100% QI ...
December 15, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27976813/evaluation-of-drug-efficacy-of-dpp-4-inhibitors-based-on-theoretical-analysis-with-pharmacokinetics-and-pharmacodynamics
#16
Risa Takayanagi, Takumi Uchida, Koji Kimura, Yasuhiko Yamada
Dipeptidyl peptidase-4 (DPP-4) inhibitors are used clinically as therapeutic agents for treatment of diabetes. To determine the rate of DPP-4 inhibition induced by these inhibitors, we used pharmacokinetic and pharmacodynamic parameters to theoretically examine the relationship between the rate of DPP-4 inhibition and clinical efficacy following administration of 4 different DPP-4 inhibitors (sitagliptin, vildagliptin, alogliptin, linagliptin) by focusing on the increase in level of glucagon-like peptide-1 (GLP-1) induced by their administration...
December 15, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27976409/oral-drug-absorption-in-pediatrics-the-intestinal-wall-its-developmental-changes-and-current-tools-for-predictions
#17
REVIEW
Jean-Marie Nicolas, François Bouzom, Hugues Chanteux, Anna-Lena Ungell
The dissolution, intestinal absorption and presystemic metabolism of a drug depend on its physicochemical characteristics but also on numerous physiological (e.g. gastrointestinal pH, volume, transit time, morphology) and biochemical factors (e.g. luminal enzymes and flora, intestinal wall enzymes and transporters). Over the last decade, evidence has accumulated indicating that these factors may differ in children and adults resulting in age-related changes in drug exposure and drug response. Thus, drug dosage may require adjustment for the pediatric population to ensure the desired therapeutic outcome and to avoid side-effects...
December 15, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27925249/inhibition-of-glucuronidation-and-oxidative-metabolism-of-buprenorphine-using-gras-compounds-or-dietary-constituents-supplements-in-vitro-proof-of-concept
#18
Neha V Maharao, Anand A Joshi, Phillip M Gerk
The present study investigated the potential of generally recognized as safe compounds or dietary substances to inhibit the presystemic metabolism of buprenorphine and increase its oral bioavailability. Using IVIVE, the buprenorphine extraction ratios in intestine and liver were predicted as 96% and 71%, respectively. In addition, the relative fraction of buprenorphine metabolized by oxidation and glucuronidation in these two organs was estimated using pooled human intestinal and liver microsomes. In both organs, oxidation appeared to be the major metabolic pathway with a six and four fold higher intrinsic clearance than glucuronidation in intestine and liver, respectively...
December 7, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27925244/the-absorption-enhancement-of-norisoboldine-in-the-duodenum-of-adjuvant-induced-arthritis-rats-involves-the-impairment-of-p-glycoprotein
#19
Cong Duan, Jiao-Mei Guo, Yue Dai, Yu-Feng Xia
Lindera aggregata (Sims) Kosterm root has been used in traditional Chinese medicine for the treatment of rheumatism palsy, dyspepsia and frequent urination for a long time. Norisoboldine, the main active constituent of this herb drug, possesses outstanding anti-arthritis activity. However, the in vivo disposition of norisoboldine is known to a limited extent, especially under the pathological condition of rheumatoid arthritis (RA). The aim of this study is to investigate whether and how the absorption of norisoboldine is altered in adjuvant-induced arthritis (AIA) rats...
January 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27925239/physiologically-based-pharmacokinetic-modeling-revealed-minimal-codeine-intestinal-metabolism-in-first-pass-removal-in-rats
#20
Keumhan Noh, Shu Chen, Qi J Yang, K Sandy Pang
The physiologically based model with segregated flow to the intestine (SFM-PBPK; partial, lower flow to enterocyte region vs. greater flow to serosal region) was found to describe the first-pass glucuronidation of morphine (M) to morphine-3β-glucuronide (MG) in rats after intraduodenal (i.d.) and intravenous (i.v.) administration better than the traditional model (TM), for which a single intestinal flow perfused the whole of the intestinal tissue. The segregated flow model (SFM) described a disproportionately greater extent of intestinal morphine glucuronidation for i...
January 2017: Biopharmaceutics & Drug Disposition
journal
journal
27820
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"