Abstract:
:The present study was undertaken to characterize the transport of (3-methyl-His(2)) thyrotropin-releasing hormone ([(3)H]MeTRH) across the blood-brain barrier in mice and the effects of thyrotropin-releasing hormone (TRH) and its analogues (taltirelin and montirelin) on the transport and brain distribution. Integration plot analysis was used to calculate the influx clearance (CL(in)) of [(3)H]MeTRH after intravenous (i.v.) injection in mice. Furthermore, the capillary depletion method was performed to determine whether [(3)H]MeTRH crossed the blood-brain barrier. The effects of TRH and its analogues on the brain distribution of [(3)H]MeTRH were also examined by co-injection with the radioligand. The brain distribution of [(3)H]MeTRH and [(14)C]sucrose increased with the time after i.v. injection in mice, and the level of [(3)H]MeTRH was significantly higher than that of [(14)C]sucrose 5 min after the injection. The CL(in) value of [(3)H]MeTRH was significantly higher than that of [(14)C]sucrose, and the value of [(3)H]MeTRH was reduced by co-injection with unlabeled MeTRH. Also, capillary depletion showed that [(3)H]MeTRH was distributed largely in the brain parenchyma and this distribution was significantly inhibited by co-injection of TRH and montirelin but not taltirelin. The present study indicates that the transport of [(3)H]MeTRH into the brain may be via a saturable process.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Urayama A,Yamada S,Ohmori Y,Deguchi Y,Uchida S,Kimura Rdoi
10.2133/dmpk.18.310subject
Has Abstractpub_date
2003-01-01 00:00:00pages
310-8issue
5eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/18.310journal_volume
18pub_type
杂志文章abstract::This exploratory retrospective study examined the effects of polymorphisms in transporter genes related to irinotecan pharmacokinetics and those in genes related to irinotecan pharmacodynamics on the efficacy of first-line combination chemotherapy with irinotecan, 5-fluorouracil, and folinic acid (leucovorin) (FOLFIRI...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.dmpk-11-rg-128
更新日期:2012-01-01 00:00:00
abstract::The ATP-binding cassette transporter, ABCG2, which is expressed at high levels in the intestine and liver, functions as an efflux transporter for many drugs, including clinically used anticancer agents such as topotecan and the active metabolite of irinotecan (SN-38). In this study, to elucidate the linkage disequilib...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.21.109
更新日期:2006-04-01 00:00:00
abstract::In a clinical setting, changes in pharmacokinetics due to drug-drug interactions can often directly affect the therapeutic safety and efficacy of drugs. Recently, interest has been shown in drug-drug interactions in the intestine. It is now recognized that changes in the functions of drug transporters substantially in...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.dmpk-12-rg-010
更新日期:2013-01-01 00:00:00
abstract::The HCT-15 human colon cancer cell line has a Na(+)-dependent carrier-mediated transport system for the uptake of glycerol. A similar transport system has been suggested to be present also in the small intestine and is of interest with regard to its role in the absorption of glycerol and possibly some structurally rel...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.22.195
更新日期:2007-06-01 00:00:00
abstract::In vivo percutaneous absorption of emedastine difumarate was investigated in rats and compared with rat skin in vitro. Since emedastine entering the systemic circulation is mostly excreted in bile, we first came up with the method of collecting bile with a minimal skin incision. In vivo skin permeation of the drug was...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.20.331
更新日期:2005-10-01 00:00:00
abstract::Maleic acid (MA) was purposefully adulterated in an array of starch-based foods in Taiwan, inciting a food safety incident. Due to limited data on the pharmacokinetics and bioavailability of ingested MA, we studied pharmacokinetic (PK) parameters in serum and urine of Sprague Dawley rats. Three groups of male and fema...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2016.09.005
更新日期:2016-12-01 00:00:00
abstract::To investigate the transport function of the blood-brain barrier (BBB), we employed an in vitro model of the BBB, consisting of a co-culture of porcine brain capillary endothelial cells (BCECs) with rat astrocytes. Porcine BCECs were cultured on a filter insert with rat astrocytes on the underlying plastic well. Rat a...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.17.34
更新日期:2002-01-01 00:00:00
abstract:UNLABELLED:Better prediction of drug disposition prior to the clinical trial is critical for the efficient development of new drugs. The purpose of this study is to develop a novel multiple assessment methodology of hepatocellular drug disposition from drug uptake to efflux including biliary and basolateral excretion, ...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2015.12.001
更新日期:2016-04-01 00:00:00
abstract::Twenty genetic variations, including seven novel ones, were found in the human SLC22A1 gene, which encodes organic cation transporter 1, from 116 Japanese individuals. The novel variations were as follows: -94C>A in the 5'-untranslated region (A of the translation start codon is numbered +1 in the cDNA sequence; MPJ6_...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.19.308
更新日期:2004-08-01 00:00:00
abstract::The hepatic uptake transporter organic anion transporting polypeptide (OATP) 1B1 is inhibited by some uremic toxins; however, direct inhibition can only partially explain the delayed systemic elimination of substrate drugs in renal failure patients. This study aimed to examine the long-lasting inhibition of OATP1B1 by...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2020.09.001
更新日期:2020-12-01 00:00:00
abstract::The purpose of the present study was to evaluate and compare the absolute protein expression levels of 28 drug-related transporters in Caco-2 cell monolayers cultured for 2, 3, and 4 weeks. Plasma membrane fractions of Caco-2 cells cultured on Transwell inserts for 2, 3 and 4 weeks were prepared and digested with tryp...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2014.11.002
更新日期:2015-04-01 00:00:00
abstract::Trimethylaminuria is caused by excessive malodorous trimethylamine excreted via urine and body secretion by decreased hepatic flavin-containing monooxygenase 3 (FMO3) metabolic capacity for transforming non-odorous trimethylamine N-oxide. This study investigates foodstuff first in healthy volunteers for palliative car...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.24.549
更新日期:2009-01-01 00:00:00
abstract::Prothrombin time (PT) has been widely used for measuring anticoagulation intensity under rivaroxaban therapy, but precise information has not been well established yet. Consecutive 96 non-valvular atrial fibrillation (NVAF) under rivaroxaban between Jan/June, 2015 were recruited. Serum concentration (SC) and PT with 5...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2018.02.002
更新日期:2018-08-01 00:00:00
abstract::The present study aims is to investigate the metabolic mechanism of Xue-Fu-Zhu-Yu decoction (XFZYD) in the treatment of blood-stasis syndrome in Coronary Heart Disease (CHD). To that end, 30 CHD patients with Blood-Stasis Syndrome (BSS) and 20 healthy subjects were enrolled. LC-Q-TOF/MS analysis determined that in com...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2019.07.004
更新日期:2019-10-01 00:00:00
abstract::Protein kinases are potential drug targets for the treatment of a variety of diseases, including cancer. In particular, specific tyrosine kinase inhibitors are rapidly being developed as new drugs for the inhibition of malignant cell growth and metastasis formation. Most of these newly developed tyrosine kinase inhibi...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2133/dmpk.25.72
更新日期:2010-01-01 00:00:00
abstract::Since porphyrins are regarded as endogenous substrates for the ATP-binding cassette (ABC) transporter ABCG2, it is hypothesized that functional impairment owing to genetic polymorphisms or inhibition of ABCG2 by drugs may result in a disruption of cellular porphyrin homeostasis. In the present study, we expressed ABCG...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.22.428
更新日期:2007-12-01 00:00:00
abstract::Pept2 knockout mice are an important tool to evaluate the evolving role and relevance of this proton-coupled oligopeptide transporter beyond drug disposition, where the transporter also modulates the pharmacodynamic and toxicodynamic effects of drug substrates. Our in vivo studies with glycylsarcosine in Pept2 knockou...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2133/dmpk.23.236
更新日期:2008-01-01 00:00:00
abstract:: Human cytochrome P450 CYP2A6 and CYP2A13 catalyze nicotine metabolisms and mediate activation of tobacco-specific carcinogens including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In this study, we found rhinacanthins A, B, and C isolated from Rhinac...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.dmpk-13-rg-048
更新日期:2014-01-01 00:00:00
abstract::MCT1(SLC16A1) is the first member of the monocarboxylate transporter (MCT) and its family is involved in the transportation of metabolically important monocarboxylates such as lactate, pyruvate, acetate and ketone bodies. This study identifies genetic variations in SLC16A1 in the ethnic Chinese group of the Singaporea...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.24.469
更新日期:2009-01-01 00:00:00
abstract::Methyl gallate (MG) and pentagalloyl glucopyranose (PGG) are bioactive phenolic compounds that possess various pharmacological activities. However, the knowledge of hepatic metabolism of MG and PGG is limited. The purpose of this study was to investigate the in vitro glucuronidation of MG and PGG using liver microsome...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2016.04.003
更新日期:2016-08-01 00:00:00
abstract::Oligopeptide transporter PEPT1 is thought to be involved in the intestinal absorption and renal reabsorption of peptides and therapeutic agents. The driving force of PEPT1 is H+ gradient, a part of which is supplied by Na+/H+ exchanger (NHE) expressed on the apical surface of the epithelium although molecular identifi...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.20.443
更新日期:2005-12-01 00:00:00
abstract::The effect of carrageenan-induced acute peripheral inflammation (API) on the pharmacokinetics of the hepatically metabolizing compound midazolam (MDZ) was investigated in rats. Rats were subcutaneously treated with λ-carrageenan in the hind paw to induce API. When MDZ was intravenously administered in male rats, it wa...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.dmpk-14-rg-020
更新日期:2014-01-01 00:00:00
abstract::Tuftsin, a natural phagocytosis-stimulating tetrapeptide, had aroused much interest in tumor immunotherapy, but the poor pharmacokinetics hampered its clinical developments, for that it was extremely susceptible to degradation by enzymolysis in vivo. T Peptide (TP) was a newly designed tuftsin derivative aimed to enha...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2015.08.005
更新日期:2016-02-01 00:00:00
abstract::Medication therapy is the first line of treatment in the management of epilepsy. Fetal exposure to valproic acid (VPA), an antiepileptic drug, poses an elevated risk of teratogenicity in early pregnancy. Some studies have reported that monocarboxylate transporters (MCTs) may be involved in the placental transport of V...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2018.03.004
更新日期:2018-12-01 00:00:00
abstract::The current EMA drug interaction guideline was published in 2012. This guideline gives important recommendations on the information required to elucidate the interaction potential of an investigational drug, both as effects of the investigational drug on the PK of other drugs and effects of other medicinal products on...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1016/j.dmpk.2019.11.005
更新日期:2020-02-01 00:00:00
abstract::Pitavastatin undergoes little hepatic metabolism but it is a substrate for uptake and efflux transporters, particularly OATP1B1 (gene SLCO1B1). A previous study in 8 Japanese healthy subjects showed that co-administration with grapefruit juice (GFJ) resulted in a small increase in systemic exposure to pitavastatin. We...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.2133/dmpk.dmpk-12-rg-067
更新日期:2013-01-01 00:00:00
abstract::Tacrolimus is a widely used immunosuppressant after organ transplantation. The narrow therapeutic window and individual variability in tacrolimus pharmacokinetics make management of this agent a great challenge. This study was undertaken to determine the association of clinical markers, cytochrome P450, family 3, subf...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.dmpk-13-rg-095
更新日期:2014-01-01 00:00:00
abstract::Genetic factors have a significant impact on the PK variability of EFV, much higher than other non-genetic factors, such as demography. In this work we have performed a comprehensive PG analysis of genes encoding the major metabolizing enzymes and transporters of EFV, establishing a clear relationship between the PK p...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2016.06.001
更新日期:2016-10-01 00:00:00
abstract::The participation of cytochrome P-450 (CYP) isoforms in the metabolism of selegiline was investigated. Experiments using recombinant CYP isoforms expressed in human lymphoblastoid cells showed CYP2B6 to be the major CYP isoform involved with the metabolism of selegiline. CYP1A2 and CYP3A4 also contributed to the metab...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.17.199
更新日期:2002-01-01 00:00:00
abstract::Polymorphic human and cynomolgus macaque flavin-containing monooxygenases (FMO) 3 are important oxygenation enzymes for nitrogen-containing drugs. Inter-animal variability of FMO3-dependent drug oxygenations in vivo is suspected in cynomolgus macaques because such variability is evident in humans. Therefore, this foll...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2020.07.001
更新日期:2020-12-01 00:00:00