journal
MENU ▼
Read by QxMD icon Read
search

Drug Metabolism and Pharmacokinetics

journal
https://www.readbyqxmd.com/read/28318878/insulin-stimulates-transport-of-organic-anion-compounds-mediated-by-organic-anion-transporting-polypeptide-2b1-in-the-human-intestinal-cell-line-caco-2
#1
Taku Kobayashi, Takahiro Koizumi, Masaki Kobayashi, Jiro Ogura, Yuichi Horiuchi, Yuki Kimura, Ayuko Kondo, Ayako Furugen, Katsuya Narumi, Natsuko Takahashi, Ken Iseki
Organic anion transporting polypeptide 2B1 (OATP2B1) is the major uptake transporter in the intestine, and transports various clinically used therapeutic agents. Insulin acts through the insulin receptor in targeted cells, and Rab8A is one of the insulin signaling pathways. The small intestine in humans also expresses insulin receptor and Rab8A. It has been reported that insulin stimulates peptide transporter 1 (PEPT1) expression at the apical membrane and increases uptake of PEPT1 substrates in small intestine epithelial model cells (Caco-2 cells)...
December 27, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28153492/sex-and-age-dependent-gene-expression-in-human-liver-an-implication-for-drug-metabolizing-enzymes
#2
Yasuhiro Uno, Ryo Takata, Go Kito, Hiroshi Yamazaki, Kazuko Nakagawa, Yusuke Nakamura, Tetsuya Kamataki, Toyomasa Katagiri
Sex and age differences in hepatic expression of drug-metabolizing enzyme genes could cause variations in drug metabolism, but has not been fully elucidated, especially in Asian population. In this study, the global expression of human hepatic genes was analyzed by microarrays in 40 Japanese subjects (27 males and 13 females). Thirty-five sex-biased genes were identified (P < 0.005). Whereas, 60 age-biased genes in two age groups, <60 years and ≥70 years (P < 0.001), were identified in males...
February 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28017537/human-leukocyte-antigen-and-idiosyncratic-adverse-drug-reactions
#3
REVIEW
Toru Usui, Dean J Naisbitt
A clinical association between a specific human leukocyte antigen (HLA) allele and idiosyncratic adverse drug reactions (IADRs) is a strong indication that IADRs are mediated by the adaptive immune system. For example, it is well-established that HLA-B*15:02 and HLA-B*57:01 are associated with carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and abacavir-induced hypersensitivity/flucloxacillin-induced liver injury, respectively. Drug-specific T-cells whose response is restricted by specific HLA risk alleles have been detected from IADR patients, also suggesting an adaptive immune pathogenesis...
February 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28129974/prediction-of-the-potential-risk-of-idiosyncratic-drug-toxicity
#4
EDITORIAL
Kousei Ito, Kaoru Kobayashi
No abstract text is available yet for this article.
December 21, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28209435/contribution-of-equilibrative-nucleoside-transporter-ent-2-to-fluorouracil-transport-in-rat-placental-trophoblast-cells
#5
Akinori Takagi, Tomohiro Nishimura, Tomoya Akashi, Masatoshi Tomi, Emi Nakashima
Fluorouracil is used for treatment of breast cancer even in pregnant women, except during fetal organogenesis. The purpose of this study was to clarify the transport mechanism of fluorouracil at the rat placental barrier. Maternal-to-fetal transfer of [(3)H]fluorouracil in rats at gestational day 19.5 was saturable and much higher than that of [(14)C]sucrose. The uptake of [(3)H]fluorouracil was also saturable in rat placental trophoblast TR-TBT 18d-1 cells, which express both equilibrative nucleoside transporter (ENT) 1 and ENT2...
December 8, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28111103/potentiation-of-the-anticoagulation-effect-of-warfarin-by-the-herbal-remedy-shu-jing-hwo-shiee-tang-in-rats-the-dosing-regimen-and-pharmacokinetic-interaction
#6
Yune-Fang Ueng, Chung-Kuang Lu, Sien-Hung Yang, Hong-Jaan Wang, Chiung-Chiao Huang
The herbal remedy Shu-Jing-Hwo-Shiee-Tang (SJHST) has been used in traditional Chinese medical care for the treatment of osteoarthritis. This study aims to examine the influence of SJHST on the oxidation and anticoagulation effect of warfarin in male rats. In three SJHST preparations (S1-S3), hesperidin, gentiopicrin, and paeoniflorin were identified as chemical marker ingredients. The inhibition of liver microsomal warfarin 7-hydroxylation (WOH) activity by 50% methanolic extracts of SJHST was potentiated by β-glucosidase pretreatment, but not by NADPH-fortified microsomal preincubation...
December 8, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27876352/quantitative-analysis-of-pharmacokinetic-profiles-of-verapamil-and-drug-drug-interactions-induced-by-a-cyp-inhibitor-using-a-stable-isotope-labeled-compound
#7
Makoto Kataoka, Chie Kojima, Kazuki Ueda, Keiko Minami, Haruki Higashino, Shinji Sakuma, Kazutaka Togashi, Kuninori Mutaguchi, Shinji Yamashita
The purpose of the present study is to demonstrate a useful approach (isotope-IV method) for analyzing drug-drug interactions (DDIs) following the oral administration of drugs using stable isotope-labeled compounds. Verapamil hydrochloride (VER) was used as a drug model. Deuterium-labeled VER (VER-d6, 0.005 mg/kg) was intravenously administered to rats with or without a pre-treatment with 1-aminobenzotriazole (ABT, 100 mg/kg), a potent CYP inhibitor, 1.5 h after the oral administration of VER (1 mg/kg)...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27839692/a-possible-role-for-hla-drb1-04-06-in-statin-related-myopathy-in-japanese-patients
#8
Kimie Sai, Kouji Kajinami, Hironobu Akao, Mizuho Iwadare, Ryoko Sato-Ishida, Yasuyuki Kawai, Kenji Takeda, Takashi Tanimoto, Takashi Yamano, Takashi Akasaka, Tatsuro Ishida, Ken-Ichi Hirata, Keijiro Saku, Shusuke Yagi, Takeshi Soeki, Masataka Sata, Masafumi Ueno, Shunichi Miyazaki, Aya Shiraki, Jun-Ichi Oyama, Koichi Node, Koichi Sugamura, Hisao Ogawa, Kouichi Kurose, Keiko Maekawa, Yumiko Matsuzawa, Takuya Imatoh, Ryuichi Hasegawa, Yoshiro Saito
Statin-related myopathy (SRM) is a clinically important adverse reaction. Recent pharmacogenetic research, mainly in non-Asian populations, have indicated clinical relevance of some of genetic biomarkers to SRM, but predictive markers for SRM in Asian populations including Japanese has not yet been established. This study was aimed to identify clinically important genetic markers associated with SRM in Japanese patients. Allele frequencies of the three reported candidate markers - SLCO1B1 rs4149056, RYR2 rs2819742, and GATM rs9806699 - and carrier frequencies of HLA types were compared between patients with SRM patients (n = 52) and healthy Japanese subjects (n = 2878 or 86 (for rs9806699) as controls)...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27839691/modeling-of-aceclofenac-metabolism-to-major-metabolites-in-healthy-volunteers
#9
Eunyoung Kim, Chunhwa Ihm, Wonku Kang
Aceclofenac has been used widely as a potent analgesic and anti-inflammatory drug. Aceclofenac is converted to 4'-hydroxyaceclofenac and diclofenac via CYP2C9-mediated hydroxylation and hydrolysis, respectively. CYP2C9 also mediates the hydroxylation of diclofenac to yield 4'-hydroxydiclofenac and the hydrolysis of 4'-hydroxyaceclofenac to 4'-hydroxydiclofenac. We aimed to model the metabolism of aceclofenac in volunteers using a compartmental modeling approach. After an oral dose of 100 mg aceclofenac in volunteers, plasma concentrations of aceclofenac and its three metabolites were measured...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27836712/application-of-substrate-depletion-assay-to-evaluation-of-cyp-isoforms-responsible-for-stereoselective-metabolism-of-carvedilol
#10
Masahiro Iwaki, Toshiro Niwa, Saya Bandoh, Megumi Itoh, Hitomi Hirose, Atsushi Kawase, Hiroshi Komura
To evaluate the relative contribution of cytochrome P450 (CYP) isoforms responsible for carvedilol (CAR) oxidation, enantioselective metabolism of CAR was investigated in human liver microsomes (HLMs) and recombinant human CYPs by using the substrate depletion assay. CYP2D6 exhibited the highest contribution to the metabolism of R-CAR, followed by CYP3A4, CYP1A2, and CYP2C9, whereas the metabolism of the S-enantiomer was mainly mediated by CYP1A2, followed by CYP2D6 and CYP3A4. In HLMs, metabolism of R- and S-CAR was markedly inhibited by quinidine; R-CAR metabolism (57-61% decrease) was more inhibited than S-CAR metabolism (37-43% decrease), and furafylline and ketoconazole almost equally inhibited metabolism of both enantiomers by 25-32% and 30-50%, respectively...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27836711/effect-of-cigarette-smoke-extract-on-p-glycoprotein-function-in-primary-cultured-and-newly-developed-alveolar-epithelial-cells
#11
Mikihisa Takano, Ryosuke Naka, Yoshihiro Sasaki, Saori Nishimoto, Ryoko Yumoto
The effect of cigarette smoke extract (CSE) on P-glycoprotein (P-gp) function in the distal lung is unclear. In this study, we first examined the expression and function of P-gp and the effect of CSE in rat primary cultured alveolar epithelial cells. The expression of P-gp protein was observed in type I-like cells, but not in type II cells. In type I-like cells, rhodamine 123 (Rho123) accumulation was enhanced by various P-gp inhibitors such as verapamil and cyclosporine A. In addition, the expression of P-gp mRNAs, mdr1a and mdr1b, as well as P-gp activity increased along with the transdifferentiation...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27829538/pharmacokinetic-drug-interaction-study-between-overactive-bladder-drugs-mirabegron-and-tolterodine-in-japanese-healthy-postmenopausal-females
#12
Yuki Nomura, Hiromi Iitsuka, Junko Toyoshima, Kentaro Kuroishi, Toshifumi Hatta, Atsunori Kaibara, Masataka Katashima, Selina Moy, Taiji Sawamoto
Mirabegron, the first selective β3-adrenoceptor agonist for the treatment of overactive bladder (OAB), inhibits cytochrome P450 isozyme CYP2D6. This study was performed in Japanese healthy postmenopausal female volunteers to assess any pharmacokinetic drug interaction between mirabegron and tolterodine, another OAB drug and a sensitive substrate of CYP2D6. Tolterodine 4 mg was orally administered from Days 1-7 and co-administered with mirabegron 50 mg from Days 8-14. Mirabegron 50 mg increased maximum concentration (Cmax) and area under the concentration-time curve from zero to 24 h after dosing (AUC24h) of tolterodine by 2...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27793475/biochemical-analysis-of-recombinant-cyp4a11-allelic-variant-enzymes-w126r-k276t-and-s353g
#13
Songhee Han, Gun-Su Cha, Young-Jin Chun, Chang Hoon Lee, Donghak Kim, Chul-Ho Yun
Human CYP4A11 is the major ω-hydroxylase of fatty acids in the liver and kidneys. It produces 20-hydroxyeicosatetraenoic acid as well as hydroxylates fatty acids. In this study, we investigated the biochemical properties of three alleles of CYP4A11: W126R, K276T, and S353G. Site-directed mutagenesis of the wild type CYP4A11 was performed, to construct the W126R, K276T, and S353G variant clones. The CYP4A11 wild type and variant constructs were heterologously expressed in Escherichia coli. CO-binding spectra showed the expression of the wild type, K276T and S353G variants, indicating the functional P450 holoenzyme...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27745731/prediction-of-cns-occupancy-of-dopamine-d2-receptor-based-on-systemic-exposure-and-in%C3%A2-vitro-experiments
#14
Kayoko Kanamitsu, Ryosuke Arakawa, Yuichi Sugiyama, Tetsuya Suhara, Hiroyuki Kusuhara
The effect of drugs in the central nervous system (CNS) is closely related to occupancy of their target receptor. In this study, we integrated plasma concentrations, in vitro/in vivo data for receptor or protein binding, and in silico data, using a physiologically based pharmacokinetic model, to examine the predictability of receptor occupancy in humans. The occupancy of the dopamine D2 receptor and the plasma concentrations of the antipsychotic drugs quetiapine and perospirone in humans were collected from the literature or produced experimentally...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27727071/developmental-regulation-of-cyp3a4-and-cyp3a7-in-chinese-han-population
#15
Hang He, Ya-Li Nie, Jiang-Feng Li, Xiang-Guang Meng, Wei-Hong Yang, Yu-Long Chen, Shu-Jie Wang, Xiaochao Ma, Quan-Cheng Kan, Li-Rong Zhang
CYP3A4 and CYP3A7 are generally served as the major adult and fetal liver forms, respectively, and exhibited a developmental switch during liver maturation. The objective of this study was to explore the potential mechanisms associated with the developmental switch of CYP3A4 and CYP3A7 in the Chinese Han population. We analyzed CYP3A4/7, nuclear receptors, and epigenetic modifications in human liver samples. We found that the expression levels of CYP3A4 mRNA in adults were significantly higher than the levels in fetus...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27720648/common-variant-of-pdz-domain-containing-1-pdzk1-gene-is-associated-with-gout-susceptibility-a-replication-study-and-meta-analysis-in-japanese-population
#16
Toshihide Higashino, Hirotaka Matsuo, Masayuki Sakiyama, Akiyoshi Nakayama, Takahiro Nakamura, Tappei Takada, Hiraku Ogata, Yusuke Kawamura, Makoto Kawaguchi, Mariko Naito, Sayo Kawai, Yuzo Takada, Hiroshi Ooyama, Hiroshi Suzuki, Nariyoshi Shinomiya
PDZ domain containing 1 (PDZK1) is a scaffold protein that organizes a transportsome and regulates several transporters' functions including urate and drug transporters. Therefore, PDZK1 in renal proximal tubules may affect serum uric acid levels through PDZK1-binding renal urate transporters. Two previous studies in Japanese male population reported that a PDZK1 single nucleotide polymorphism (SNP), rs12129861, was not associated with gout. In the present study, we performed a further association analysis between gout and rs12129861 in a different large-scale Japanese male population and a meta-analysis with previous Japanese population studies...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28109684/increase-in-the-systemic-exposure-of-primary-metabolites-of-midazolam-in-rat-arising-from-cyp-inhibition-or-hepatic-dysfunction
#17
Tsubasa Hasegawa, Satomi Nakanishi, Keiko Minami, Haruki Higashino, Makoto Kataoka, Yoshihisa Shitara, Shinji Yamashita
The main purpose of this study is to demonstrate the possibility of increase in the systemic exposure of drug metabolites by CYP-inhibition or acute hepatitis. Midazolam (MDZ) was used as a model substrate of CYP3A and 1-aminobenzotriazole (ABT) was used as a CYP-inhibitor. After oral pretreatment with ABT, MDZ was intravenously injected to rats and the plasma profiles of MDZ and its primary metabolites, 1'-hydroxy MDZ and 4-hydroxy MDZ, were observed. In the ABT-pretreatment rats, plasma AUCs of both metabolites were much larger than those in control rats, demonstrating a higher systemic exposure of metabolites under CYP-inhibited condition...
November 23, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28017536/toxicological-potential-of-acyl-glucuronides-and-its-assessment
#18
REVIEW
Atsushi Iwamura, Miki Nakajima, Shingo Oda, Tsuyoshi Yokoi
Idiosyncratic drug toxicity (IDT) is a serious problem in drug development. Reactive metabolites are postulated to be one of the causes for IDT. Conjugated metabolites are generally non-reactive except for acyl glucuronides (AGs), which are sufficiently reactive to covalently bind to endogenous proteins. Thus, it has been suggested that AGs would contribute to IDT caused by carboxylic acid-containing drugs. Glucuronidation of a carboxylate residue is catalyzed by UDP-glucuronosyltransferase 1A and 2B isoforms...
November 23, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28190756/organic-anion-transporting-polypeptide-oatp-2b1-contributes-to-the-cellular-uptake-of-theaflavin
#19
Ayuko Kondo, Katsuya Narumi, Jiro Ogura, Ai Sasaki, Keisuke Yabe, Taku Kobayashi, Ayako Furugen, Masaki Kobayashi, Ken Iseki
Organic anion-transporting polypeptide (OATP) 2B1 has been reported in the apical membranes of the human small intestinal epithelium, where it contributes to the intestinal absorption of pharmacologically active drugs. To investigate the potential for OATP2B1-mediated drug-food interactions, the effects of several polyphenolic compounds on OATP2B1-mediated estrone-3-sulfate (E3S) transport were studied by using OATP2B1-expressing HEK293 cells. Our results showed that some compounds, especially theaflavin, were strong inhibitors of OATP2B1-mediated E3S uptake...
November 22, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28129975/the-role-of-quantitative-systems-pharmacology-modeling-in-the-prediction-and-explanation-of-idiosyncratic-drug-induced-liver-injury
#20
REVIEW
Jeffrey L Woodhead, Paul B Watkins, Brett A Howell, Scott Q Siler, Lisl K M Shoda
Idiosyncratic drug-induced liver injury (iDILI) is a serious concern in drug development. The rarity and multifactorial nature of iDILI makes it difficult to predict and explain. Recently, human leukocyte antigen (HLA) allele associations have provided strong support for a role of an adaptive immune response in the pathogenesis of many iDILI cases; however, it is likely that an adaptive immune attack requires several preceding events. Quantitative systems pharmacology (QSP), an in silico modeling technique that leverages known physiology and the results of in vitro experiments in order to make predictions about how drugs affect biological processes, is proposed as a potentially useful tool for predicting and explaining critical events that likely precede immune-mediated iDILI, as well as the immune attack itself...
November 21, 2016: Drug Metabolism and Pharmacokinetics
journal
journal
40362
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"