Abstract:
:Utilization of nitric oxide (NO) synthase (NOS) inhibitors to probe the role of NO in various central nervous system processes requires use of an inhibitor selective for neuronal NOS, and is facilitated by knowledge of the pharmacokinetics of the inhibitor. The present project was undertaken to elucidate the disposition of the selective neuronal NOS inhibitor 7-nitroindazole (7-NI). A simple, specific HPLC assay was developed with requisite sensitivity to quantitate 7-NI in serum after administration of pharmacologically relevant doses. Further experiments were performed to assess the effects of administered dose on 7-NI disposition. 7-NI displayed marked nonlinearity, consistent with saturable elimination, when administered by ip injection in peanut oil. The nonlinearity was related to total dose, but not to the concentration of 7-NI in the vehicle. Binding of 7-NI in rat serum was concentration-independent and does not contribute to the nonlinearity. Various formulations for iv administration of this water-insoluble compound were evaluated; the optimal vehicle, from the standpoint of 7-NI solubility, appeared to inhibit the clearance of 7-NI from the systemic circulation. Considering the nonlinear disposition of 7-NI, knowledge of the pharmacokinetics of this inhibitor is requisite to designing administration protocols to achieve the desired magnitude and duration of NOS inhibition.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
Bush MA,Pollack GMdoi
10.1002/bdd.230keywords:
subject
Has Abstractpub_date
2000-09-01 00:00:00pages
221-8issue
6eissn
0142-2782issn
1099-081Xpii
10.1002/bdd.230journal_volume
21pub_type
杂志文章abstract::A three-way crossover study in 18 healthy male volunteers was conducted to evaluate the bioequivalence of three different 200 mg anhydrous theophylline immediate-release (IR) capsules. The products had not been rated as therapeutically equivalent by the US Food and Drug Administration (FDA) owing to a lack of bioequiv...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/1099-081x(199912)20:9<417::aid-bdd205>3.0.
更新日期:1999-12-01 00:00:00
abstract::Previous studies have shown that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment (2.56 nmol/kg i.p. daily×4) increased PepT1, Mrp2, Mrp4, Asbt, but not Mdr1/P-gp in the rat small intestine. In this study, the intestinal everted sac technique, together with various select probes: mannitol (paracellular transport), gl...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.742
更新日期:2011-03-01 00:00:00
abstract::An evaluation of the literature indicated that certain aspects of the disposition kinetics of iothalamate, important to the accurate determination of glomerular filtration rate in dogs and humans, remain to be resolved. The simultaneous clearances of iothalamate and inulin in 5 dogs were determined at three steady-sta...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510070405
更新日期:1986-07-01 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::The utility of pyrazinamide (PZA) in the short-course antituberculous treatment is well established. All available data support the idea that the PZA metabolite pyrazinoic acid (PA) is the active compound against M. tuberculosis. This situation warranted a deeper investigation of possible interactions with respect to ...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.305
更新日期:2002-07-01 00:00:00
abstract::Multidrug resistance (MDR) is common in patients and has been linked to transforming growth factor-β1 (TGF-β1) and overexpression of drug efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), although the molecular mechanisms remain largely unknown. This study aimed to investigate the ...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2172
更新日期:2019-02-01 00:00:00
abstract::A high-performance liquid chromatographic method was developed to determine stobadin pharmacokinetics in dog and man. The relative bioavailability of stobadin dipalmitate compared with dihydrochloride was 46.4 per cent in dog. In man peak serum concentrations ranged from 12 to 289 ng ml-1 after a single oral dose of s...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510120104
更新日期:1991-01-01 00:00:00
abstract::Comparative in vivo studies of aqueous solution, multiple w/o/w, and w/o emulsions showed that formulating 5-fluorouracil in emulsion systems significantly sustained the release of the drug from intramuscular injection sites in the rat. Intramuscular injection of the drug in both w/o and w/o/w emulsion systems produce...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510100305
更新日期:1989-05-01 00:00:00
abstract::The objective of this study was to assess the effect of dietary fibers on the transport of losartan, an angiotensin II type 1 receptor blocker, in small intestinal cells. Using Caco-2 cells in vitro, losartan uptake and transport were evaluated in the presence of various fibers (cellulose, chitosan, sodium alginate an...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2004
更新日期:2016-05-01 00:00:00
abstract::The effect of the combination of a new anticonvulsant drug HEPP and carbamazepine (CBZ) on the pharmacokinetics of HEPP and CBZ was investigated using rabbits as an animal model. The study was performed in 18 male New Zealand white rabbits which were randomly divided into three groups, according to a balanced incomple...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.356
更新日期:2003-07-01 00:00:00
abstract::Ritalin, an immediate release form of racemic methylphenidate hydrochloride, has been available in the USA since 1955 and is used for the treatment of ADHD. The objective of this study was to evaluate the pharmacokinetics of modified-release methylphenidate (highest single dose), Ritalin LA, when administered under fa...
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.358
更新日期:2003-09-01 00:00:00
abstract::Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin ...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2055
更新日期:2017-01-01 00:00:00
abstract::The pharmacokinetics of an intravenous injection of disopyramide was studied in five normal subjects and six patients with varying degrees of renal impairment. The elimination rate constant (beta) was related to the endogenous creatinine clearance (Clcr). However, a decrease in beta was not observed until the Clcr was...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510010308
更新日期:1980-01-01 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::The steady-state pharmacokinetics of an ultralong sustained release formulation of theophylline (Unilong) twice daily (bid) in elderly hospitalized patients suffering from chronic obstructive pulmonary disease (COPD) have been studied in order to establish guidelines for monitoring. The study was carried out in 37 pat...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,指南,杂志文章,实务指引
doi:10.1002/bdd.354
更新日期:2003-05-01 00:00:00
abstract::Macelignan is a natural phenolic compound that possesses many types of health benefits such as antiinflammation. This study aimed to characterize the metabolism of macelignan via the glucuronidation pathway and to identify the main UGT enzymes involved in macelignan glucuronidation. The rates of glucuronidation were d...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.1914
更新日期:2014-12-01 00:00:00
abstract::The pharmacokinetic behavior of glycyrrhizin in four patients with acute hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis group) receiving chronically an IV administration of a 120 mg dose once a day or once every other day of glycyrrhizin was investigated. The plasma concentration of glycy...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章
doi:10.1002/bdd.2510160103
更新日期:1995-01-01 00:00:00
abstract::The aim of this investigation was to assess the pharmacokinetic properties of high-dose menadione (VK3), as an anticancer agent, in plasma and red blood cells (RBCs) in rabbits. An extremely high dose of 75 mg menadiol sodium diphosphate (Synkayvite) was intravenously injected. HPLC analysis was applied to measure the...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
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更新日期:1996-08-01 00:00:00
abstract::Acute viral infection has long been recognized to down-regulate cytochrome P-450 enzymes and subsequently to result in changes in the pharmacological and toxicological responses to xenobiotics. In our previous research, chronic retrovirus infection induced by inoculating a susceptible strain of mice with LP-BM5 murine...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/(sici)1099-081x(199801)19:1<9::aid-bdd70>3
更新日期:1998-01-01 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::CYP2C9 is a human microsomal cytochrome P450c (CYP). Much variation in CYP2C9 levels and activity can be attributed to polymorphisms of this gene. Wild-type CYP2C9 and ten mutants were co-expressed with NADPH-cytochrome P450 reductase in Escherichia coli. The hydroxylase activities toward steroids were examined. CYP2C...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2153
更新日期:2018-09-01 00:00:00
abstract::The pharmacokinetics of a series of novel cyclic, non-peptide inhibitors of HIV protease were studied in rats or dogs after intravenous and oral administration. Six symmetrically substituted cyclic urea compounds (XK234, XM311, XM320, XM321, XM323, and XM412), which effectively inhibited HIV virus replication, with IC...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510150702
更新日期:1994-10-01 00:00:00
abstract::We report here the effect of histamine on amylase secretion in isolated lobules from the rat pancreas. Different concentrations of histamine increased amylase secretion, while the stimulatory effect was reduced by cimetidine although not by chlorpheniramine. These findings suggest that pancreatic lobules have H2 recep...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510130508
更新日期:1992-07-01 00:00:00
abstract::A pharmacokinetic study of sachets containing nalidixic acid (0.66 g) associated with sodium citrate (3.75 g)--NSC--was carried out in 10 healthy volunteers in order to determine the influence of the urine alcalinization due to sodium citrate on the elimination of nalidixic acid (NA) and its 7-hydroxy (HNA) and 7-carb...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510050303
更新日期:1984-07-01 00:00:00
abstract::The relative lung and systemic bioavailability of sodium cromoglycate following inhalation by different methods have been determined using a urinary excretion pharmacokinetic method. On three separate randomised study days, 7 days apart, subjects inhaled (i) 4x5 mg from an Intal metered dose inhaler (MDI), (ii) 4x5 mg...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::This review offers a detailed discussion of the interaction between pharmaceutical compounds and vehicles using the affinity capillary electrophoresis and the microemulsion electrokinetic chromatography. Partition coefficients of drugs were calculated between a micelle and an aqueous phases from the measurement of the...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章,评审
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更新日期:2001-10-01 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
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更新日期:1986-01-01 00:00:00
abstract::Previously we demonstrated that a hydrophilic HMG-CoA reductase inhibitor, pravastatin, was actively taken up by the liver via the 'multispecific anion transporter' using isolated rat hepatocytes (M. Yamazaki, H. Suzuki, M. Hanano, T. Tokui, T. Komai, and Y. Sugiyama, Am. J. Physiol., 264, G36-G44 (1993)). Such a carr...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/(SICI)1099-081X(199612)17:9<775::AID-BDD99
更新日期:1996-12-01 00:00:00
abstract::Ciclesonide, a new corticosteroid for allergic rhinitis, is administered as an inactive parent compound that is converted by esterases to the pharmacologically active metabolite, desisobutyryl-ciclesonide (des-CIC). This study investigated the in vitro activation of ciclesonide in nasal mucosa of multiple animal speci...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.531
更新日期:2007-03-01 00:00:00
abstract::The lipophilic weak base amodiaquine is an antimalarial drug that has been in use for over 40 years. Little is known of amodiaquine's mechanism of transport across membranes. Transport experiments of amodiaquine in Caco-2 cells showed a low recovery of 30% and rapid disappearance from the apical chamber. Compounds str...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.616
更新日期:2008-09-01 00:00:00