Abstract：
:The present study aimed to examine the potential pharmacokinetic drug interaction between valsartan and gemfibrozil. Compared with the control given valsartan (10 mg/kg) alone, the concurrent use of gemfibrozil (10 mg/kg) significantly (p < 0.05) increased the oral exposure of valsartan in rats. In the presence of gemfibrozil, the Cmax and AUC of oral valsartan increased by 1.7- and 2.5-fold, respectively. Consequently, the oral bioavailability of valsartan was significantly higher (p < 0.05) in the presence of gemfibrozil compared with that of the control group. Furthermore, the intravenous pharmacokinetics of valsartan (1 mg/kg) was also altered by pretreatment with oral gemfibrozil (10 mg/kg). The plasma clearance of valsartan was decreased by two-fold in the presence of gemfibrozil, while the plasma half-life was not altered. In contrast, both the oral and intravenous pharmacokinetics of gemfibrozil were not affected by the concurrent use of valsartan. The cellular uptake of valsartan and gemfibrozil was also investigated by using cells overexpressing OATP1B1 or OATP1B3. Gemfibrozil and gemfibrozil 1-O-β glucuronide inhibited the cellular uptake of valsartan with IC50 values (µm) of 39.3 and 20.4, respectively, in MDCK/OATP1B1, while they were less interactive with OATP1B3. The cellular uptake of gemfibrozil was not affected by co-incubation with valsartan in both cells. Taken together, the present study suggests the potential drug interaction between valsartan and gemfibrozil, at least in part, via the OATP1B1-mediated transport pathways during hepatic uptake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
Yang SJ,Kim BJ,Mo L,Han HKdoi
10.1002/bdd.2001subject
Has Abstractpub_date
2016-07-01 00:00:00pages
245-51issue
5eissn
0142-2782issn
1099-081Xjournal_volume
37pub_type
杂志文章abstract：:The mechanism of intestinal transport of valacyclovir (VACV), the L-valyl ester prodrug of acyclovir, was investigated in rats using an in situ intestinal perfusion technique. VACV demonstrates an oral bioavailability that is three to five time greater than acyclovir, concentration dependent, and saturable in humans. ...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/(sici)1099-081x(199805)19:4<209::aid-bdd93
更新日期：1998-05-01 00:00:00
abstract：:The definitions of mean residence time of drug molecules in the body (MRT) from the literature are reviewed. A formal definition of MRT, based on excretion of drug molecules and amount of drug, a parameter which is independent of constancy of both clearance and volume of distribution, is introduced and compared to oth...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.2510080304
更新日期：1987-05-01 00:00:00
abstract：:Aim. To study the pharmacokinetics of dihydroartemisinin (DHA) in Artekin (compound dihydroartemisinin) tablets in Chinese healthy volunteers. Methods. Eighteen healthy volunteers (9 males, 9 females) received Artekin tablets for oral administration. The plasma samples of DHA were analysed by liquid-liquid extraction ...
journal_title：Biopharmaceutics & drug disposition
pub_type： 临床试验,杂志文章
doi：10.1002/bdd.607
更新日期：2008-05-01 00:00:00
abstract：:The effects of age on hepatic microsomal enzyme induction were studied in male CD-1 mice. Six week old and 1 year old animals were treated with either phenobarbital (80 mg kg-1) or saline once daily for 3d. Twenty-four hours after the last treatment, animals were sacrificed and livers were harvested. Hepatic microsoma...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/(sici)1099-081x(199703)18:2<139::aid-bdd7>
更新日期：1997-03-01 00:00:00
abstract：:After in vitro incubation of cecal content from CVL or gnotobiotic rats with rhein anthraquinone (1 mg g-1) for 18 h at 37 degrees, the anthraquinone was converted to rhein anthrone for 23.5 (SD +/- 3.4) per cent and 19.4 (+/- 4.7) per cent, respectively. Liquid cultures of some strictly anaerobic fecal bacteria of ma...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.2510130403
更新日期：1992-05-01 00:00:00
abstract：:The pharmacokinetics and the dose proportionality of a new anticonvulsant compound, HEPP (D,L-3-hydroxy-3-ethyl-3-phenylpropionamide) was studied in healthy male volunteers as part of the pharmacological evaluation for new drugs. Study was performed administering doses of 250, 375, 500 and 625 mg of HEPP to six male v...
journal_title：Biopharmaceutics & drug disposition
pub_type： 临床试验,杂志文章
doi：10.1002/(sici)1099-081x(199812)19:9<583::aid-bdd13
更新日期：1998-12-01 00:00:00
abstract：:Two studies are reported that assess the bioequivalence of a new half-strength drug combination containing 25 mg hydrochlorothiazide and 37.5 mg triamterene compared to a full-strength formulation containing 50 mg hydrochlorothiazide and 75 mg triamterene. The first study (I) compared the absorption and disposition of...
journal_title：Biopharmaceutics & drug disposition
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/bdd.2510110308
更新日期：1990-04-01 00:00:00
abstract：:A major component of physiologically based pharmacokinetic (PBPK) models is the 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 pe...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.2072
更新日期：2017-03-01 00:00:00
abstract：:The biotransformation of thionorphine (N-cyclopropylmethyl-7alpha-[(s)-1-hydroxy-1-methyl-3-(2thiophene)-propyl]-6,14-endo-ethano tetrahydrooripavine), a new analgesic, was in-vestigated in rats. The results of metabolite analysis by liquid chromatography/electrospray ionization tandem mass spectrometry with positive ...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.360
更新日期：2004-04-01 00:00:00
abstract：:Loxoprofen (LX) is a prodrug-type non-steroidal anti-inflammatory drug which is used not only as an oral drug but also as a transdermal formulation. As a pharmacologically active metabolite, the trans-alcohol form of LX (trans-OH form) is generated after oral administration to humans. The objectives of this study were...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.1945
更新日期：2015-09-01 00:00:00
abstract：PURPOSE:Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. It was hypothesized that amifostine may be a good candidate for reg...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.380
更新日期：2004-01-01 00:00:00
abstract：:The urinary elimination of 4-hydroxyamphetamine (PHA) and a series of homologous 4-alkoxy-substituted amphetamines and their metabolites was examined after single and multiple oral administration to pregnant and non-pregnant mice. The metabolic profile and extent of biotransformation in a series of alkoxy analogues we...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.2510140807
更新日期：1993-11-01 00:00:00
abstract：:This study aims to characterize the pharmacodynamic properties of denosumab, a RANK ligand inhibitor, and ibandronate, a bisphosphonate, using an integrated bone homeostasis model in postmenopausal women. Mean temporal profiles of denosumab, serum and urine N-telopeptide (sNTX, uNTX), lumbar spine bone mineral density...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章,随机对照试验
doi：10.1002/bdd.770
更新日期：2011-11-01 00:00:00
abstract：:The aim of this study was to determine whether the dose influences the distribution kinetics of ciprofloxacin and ofloxacin in muscle- bone- and skin-tissues included in the isolated hindlimb of the rat. Experiments were carried out in the isolated perfused hindlimb of the rat, administering a single dose of 45, 450 o...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.245
更新日期：2000-11-01 00:00:00
abstract：:A relative bioavailability study of conventional tablet of propranolol hydrochloride was conducted in a group of 18 healthy volunteers employing the innovator's product as the reference tablet formation. Based on plasma levels of propranolol for the 24 h following administration of 2 x 40 mg oral propranolol hydrochlo...
journal_title：Biopharmaceutics & drug disposition
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/bdd.2510030204
更新日期：1982-04-01 00:00:00
abstract：:In order to examine a potential interaction between isoxicam and propranolol, single 200 mg doses of isoxicam were administered to ten healthy male volunteers before and during treatment with propranolol, gradually attaining a dose of 80 mg t.i.d. for 11 days. The pharmacokinetic profiles of the isoxicam plasma concen...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.2510070109
更新日期：1986-01-01 00:00:00
abstract：:This study was conducted to determine the relative bioavailability of Dilacor XR capsules compared to Cardizem CD capsules at both low (180 mg d-1) and high (540 mg d-1) dose levels. Trough and serial plasma samples were obtained and pharmacokinetic parameters were calculated from the steady state concentration-time p...
journal_title：Biopharmaceutics & drug disposition
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/(SICI)1099-081X(199601)17:1<43::AID-BDD935
更新日期：1996-01-01 00:00:00
abstract：:Many marketed drugs are chiral and are administered as the racemate, a 50:50 combination of two enantiomers. Pharmacodynamic and pharmacokinetic differences between enantiomers are well documented. Because of enantioselectivity in pharmacokinetics, results of in vitro pharmacodynamic studies involving enantiomers may ...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章,评审
doi：10.1002/bdd.517
更新日期：2006-11-01 00:00:00
abstract：:Effects of concomitant colestipol administration on plasma concentrations of diltiazem and desacetyldiltiazem from immediate-release (IR) and sustained-release (SR) formulations were assessed in two studies. In the first study, 12 subjects received 120-mg diltiazem hydrochloride (diltiazem) SR capsules or 120-mg dilti...
journal_title：Biopharmaceutics & drug disposition
pub_type： 临床试验,杂志文章
doi：10.1002/bdd.330
更新日期：2002-12-01 00:00:00
abstract：:Lumefantrine has been reported to be mainly bio-transformed by cytochrome P450 isozyme 3A4 to desbutyl-lumefantrine (DLF) in human liver microsomes. Since CYP3A is expressed in a sex specific manner in rats, it could be expected that the pharmacokinetics of lumefantrine would be changed in male rats compared with thos...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.1786
更新日期：2012-05-01 00:00:00
abstract：:Mivacurium, a non-depolarizing neuromuscular blocking agent, consists of three isomers; trans-trans (57%), cis-trans (36%) and cis-cis (7%). The purpose of this study was to characterize the pharmacokinetics and pharmacodynamics of mivacurium after various inputs. Four beagle dogs weighing between 7.95 and 9.89 kg wer...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/(sici)1099-081x(1998110)19:8<485::aid-bdd1
更新日期：1998-11-01 00:00:00
abstract：:Based on the principle of superposition an expression has been established relating a drug concentration at steady-state to a concentration after a single dose. This relationship applies for drugs with linear pharmacokinetics given at equal dosage intervals and it is independent of the route of administration. The rel...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.2510030302
更新日期：1982-07-01 00:00:00
abstract：:Acyl glucuronidation is the major metabolic conjugation reaction of most carboxylic acid drugs in mammals. The physiological consequences of this biotransformation have been investigated incompletely but include effects on drug metabolism, protein binding, distribution and clearance that impact upon pharmacological an...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章,评审
doi：10.1002/bdd.720
更新日期：2010-10-01 00:00:00
abstract：:The purpose of this project was to develop and validate a pharmacokinetic model and to quantify the rate and extent of distribution between plasma and skin of two beta-lactam antibiotics, amoxicillin (AMX) and cefuroxime (CFX), which are frequently administered systemically to treat skin and skin structure infections....
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.658
更新日期：2009-09-01 00:00:00
abstract：:Methotrexate (MTX) is an anchor drug used to treat rheumatoid arthritis (RA), but responsiveness is variable in effectiveness and toxicity. Methotrexate and its polyglutamate conjugates (MTXPG(n)) in red blood cells (RBC) have been associated with patient response. In the current study, 13 collagen-induced arthritic (...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.1838
更新日期：2013-05-01 00:00:00
abstract：:Biliary clearance (Clb) of sotalol (STL) enantiomers was assessed in anaesthetized Sprague-Dawley rats (419 +/- 9 g, mean +/- SEM, n = 4) following administration of a 10 mg kg-1 i.v. dose of the racemate. Clb for S- and R-STL (0.0675 +/- 0.0090 and 0.0662 +/- 0.0089 mL min-1 kg-1, respectively) represented approximat...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/(SICI)1099-081X(199611)17:8<725::AID-BDD99
更新日期：1996-11-01 00:00:00
abstract：:Non-steroidal anti-inflammatory drugs (NSAIDs) are used widely to relieve pain and to decrease inflammation. Several clinical studies have reported that NSAIDs inhibit uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes. Therefore, the study evaluated the inhibitory potential of 15 NSAIDs on the activities of s...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.1933
更新日期：2015-05-01 00:00:00
abstract：:In this comparative bioavailability study two sustained release capsule formulations of propranolol, one a clinical trial formulation and the other the U.K. sales formulation ('Inderal' LA), were compared with a conventional 'Inderal' tablet. Twelve healthy adult male volunteers received, on cross-over basis, on three...
journal_title：Biopharmaceutics & drug disposition
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/bdd.2510020105
更新日期：1981-01-01 00:00:00
abstract：:The systemic availability of a solid dispersion (coevaporate) of clofazimine (CLF) in poly(vinyl methyl ether maleic anhydride) copolymer (PVM/MA) was tested in the pig. Single 100 mg oral doses of the coevaporate and the commercial product, Lamprene (Ciba-Geigy) were administered on separate occasions (separated by a...
journal_title：Biopharmaceutics & drug disposition
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/bdd.2510150407
更新日期：1994-05-01 00:00:00
abstract：:The inhibition of rat hepatic mitochondrial aldehyde dehydrogenase (ALDH) isozymes was studied in apparent steady-state conditions after repeated intra-peritoneal cyanamide administration. The low-Km mitochondrial ALDH isozyme was more susceptible to cyanamide-induced inhibition (DI50 = 0.104 mg kg-1) than the high-Km...
journal_title：Biopharmaceutics & drug disposition
pub_type： 杂志文章
doi：10.1002/bdd.2510140508
更新日期：1993-07-01 00:00:00
