Biopharmaceutics and Drug Disposition This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Inhibition of Glucuronidation and Oxidative Metabolism of Buprenorphine Using GRAS Compounds or Dietary Constituents/Supplements: In Vitro Proof of Concept
Abstract 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 clearan...
Source: Biopharmaceutics and Drug Disposition - December 6, 2016 Category: Drugs & Pharmacology Authors: Neha V. Maharao, Anand A. Joshi, Phillip M. Gerk Tags: Special Issue Article Source Type: research

Role of ABC transporters in trans ‐epithelial transport of vitamin K antagonists
In conclusion, intestinal transfer of indanedione derivatives and acenocoumarol could be influenced by transport protein of the ABC superfamily. Coumarin derivatives are poor inhibitors of these proteins and AVKs have slight effect on mRNA ABC transporter expression level. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - December 6, 2016 Category: Drugs & Pharmacology Authors: Bernadette Espana, Solange Couturier, Caroline Prouillac Tags: Original Paper Source Type: research

Physiologically ‐Based Pharmacokinetic Modeling Revealed Minimal Codeine Intestinal Metabolism in First‐Pass Removal in Rats
We presently applied the same PBPK modeling approaches to examine the contributions of the intestine and liver on first‐pass metabolism of the precursor, codeine (C, 3‐methylmorphine) in the rat. Unexpectedly, profiles of C, M, and MG in whole blood, bile and urine, assayed by LCMS, were equally well described by both the TM‐PBPK and SFM‐PBPK. The fitted parameters for the models were similar, and the net formation intrinsic clearance of M (from C) for the liver was much higher, being 9‐ to 13‐fold that of the intestine. Simulations, based on absence of intestinal formation of M, correlated well with observatio...
Source: Biopharmaceutics and Drug Disposition - December 6, 2016 Category: Drugs & Pharmacology Authors: Keumhan Noh, Shu Chen, Qi J. Yang, K. Sandy Pang Tags: Original Paper Source Type: research

The absorption enhancement of norisoboldine in the duodenum of adjuvant ‐induced arthritis rats involves the impairment of P‐glycoprotein
Abstract Lindera aggregate (Sims) Kosterm root has been used in traditional Chinese medicine for the treatment of rheumatism palsy, dyspepsia and frequent urination for a long history. Norisoboldine (NOR), the main active constituent of this herb drug, possesses outstanding anti‐arthritis activity. However, in vivo disposition of NOR has been 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 NOR is altered in adjuvant‐induced arthritis (AIA) rats. Comparative studies of the intestine absorption o...
Source: Biopharmaceutics and Drug Disposition - December 6, 2016 Category: Drugs & Pharmacology Authors: Cong Duan, Jiao ‐Mei Guo, Yue Dai, Yu‐Feng Xia Tags: Short Communication Source Type: research

Comparing Early Liver Graft Function From Heart Beating and Living ‐Donors: A Pilot Study Aiming to Identify New Biomarkers of Liver Injury
Conclusions: ROC clearance was reduced and GGT were higher in the HBD group of longer cold ischemic times, and HBD patients performed worse than the LD group during the neophase. The HBD group further showed higher clusters of bile acids, phospholipids and lipid ω‐oxidation products, suggesting that these, ROC CL and GGT expression could serve as sensitive indices of early graft function. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Qi Joy Yang, Michael Kluger, Krzysztof Gory ński, Janusz Pawliszyn, Barbara Bojko, Ai‐ming Yu, Keumhan Noh, Markus Selzner, Angela Jerath, Stuart McCluskey, K. Sandy Pang, Marcin Wąsowicz Tags: Original Paper Source Type: research

Levofloxacin effect on erlotinib absorption. Evaluation of the interaction in undernutrition situations through population pharmacokinetic analysis in rats.
ABSTRACT 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. A passive absorption and an active secretion process b...
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Alejandro P érez Pitarch, Beatriz Guglieri‐López, Amparo Nacher, Virginia Merino, Matilde Merino‐Sanjuan Tags: Original Paper Source Type: research

Absorption, distribution, and excretion of the anti ‐tuberculosis drug delamanid in rats: Extensive tissue distribution suggests potential therapeutic value for extrapulmonary tuberculosis
ABSTRACT Delamanid (OPC‐67683, DeltybaTM, 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 14C‐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. In additi...
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Masakazu Shibata, Yoshihiko Shimokawa, Katsunori Sasahara, Noriaki Yoda, Hiroyuki Sasabe, Mitsunari Suzuki, Ken Umehara Tags: Original Paper Source Type: research

Prediction of Liver Volume – a population‐based approach to meta‐analysis of pediatric, adult and geriatric populations ‐ an update.
Conclusion: Extension and re‐parameterisation of the existing Johnson model adequately describes changes in liver volume using the body surface area in all investigated populations. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Ben G Small, Bernd Wendt, Masoud Jamei, Trevor N Johnson Tags: Original Paper Source Type: research

Quantifying Gut Wall Metabolism: Methodology Matters
ABSTRACT BackgroundOral 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. This disregard of intestinal metabolism is therefore not due to lack of available in vitro to...
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Oliver J. D. Hatley, Christopher R. Jones, Aleksandra Galetin, Amin Rostami ‐Hodjegan Tags: Special Issue Article Source Type: research

Prioritizing pharmacokinetic drug interaction precipitants in natural products: application to OATP inhibitors in grapefruit juice
Abstract 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 constit...
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Emily J. Johnson, Christina S. Won, Kathleen K öeck, Mary F. Paine Tags: Special Issue Article Source Type: research

Physiologically ‐based Pharmacokinetic Predictions of Intestinal BCRP‐Mediated Effect of Telmisartan on the Pharmacokinetics of Rosuvastatin in Humans
Abstract 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 (8...
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Soo Hyeon Bae, Wan ‐Su Park, Seunghoon Han, Gab‐jin Park, Jongtae Lee, Taegon Hong, Sangil Jeon, Dong‐Seok Yim Tags: Original Paper Source Type: research

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 of inhibitor and staggering the dose of substrate
This study also emphasises a need to account for inter‐individual variability in the gut wall and systemic exposure of inhibitors with physicochemical properties similar to KTZ, in particular in their rate of oral absorption and when using different pharmaceutical formulations, in designing and evaluating the extent of drug – drug interactions. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Bo Liu, H. Kim Crewe, Mahmut Ozdemir, Karen Rowland Yeo, Geoffrey Tucker, Amin Rostami ‐Hodjegan Tags: Original Paper Source Type: research

Unequivocal Evidence Supporting the Segregated Flow Intestinal Model that Discriminates Intestine versus Liver First ‐Pass Removal in PBPK Modeling
Abstract 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 (fQQI) 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. The SFM model was able to explain the lower extents o...
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: K. Sandy Pang, Qi Joy Yang, Keumhan Noh Tags: Special Issue Article Source Type: research

Puerarin offsets the anticoagulation effect of Warfarin in rats by inducing rCyps, upregulating vitamin K epoxide reductase and inhibiting thrombomodulin
ConclusionPuerarin increased warfarin metabolism and offset warfarin anticoagulation by inducing rCyps, upregulating VKOR and inhibiting TM in rats. The clinical impact of such potential interactions warrants further verification. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Authors: Beikang Ge, Zhen Zhang, Teddy Taining Lam, Zhong Zuo Tags: Original Paper Source Type: research

Issue Information ‐ JIP
No abstract is available for this article. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - November 30, 2016 Category: Drugs & Pharmacology Tags: Issue Information ‐ JIP Source Type: research