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 (BMD) following denosumab administration, and urine C-telopeptide (uCTX) and lumbar spine BMD upon ibandronate administration were extracted from the literature. A mechanistic model was developed that integrates denosumab pharmacokinetics with binding to RANK ligand and ibandronate inhibition of osteoclast precursor differentiation to active osteoclasts (AOC). Biomarker concentrations were linked to the AOC pool. The BMD was characterized by a turnover model with stimulation of bone formation and degradation by AOB (active osteoblasts) and AOC pools. The estimated basal sNTX, uNTX and uCTX concentrations were 7.24 nm, 14.4 nmol/mmolCr and 31µg/mmolCr. The BMD degradation rate was 0.00161 day(-1) with stimulation constants associated with AOB and AOC of 1214 and 790 pm(-1) . The plasma ibandronate concentration producing 50% of maximum inhibition of osteoclast differentiation was 522 ng/l. The integrated model, which incorporates multiple pathways of therapeutic intervention, quantitatively describes changes in clinical biomarkers of bone turnover and BMD after denosumab and ibandronate exposures in postmenopausal women.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
Marathe DD,Marathe A,Mager DEdoi
10.1002/bdd.770subject
Has Abstractpub_date
2011-11-01 00:00:00pages
471-81issue
8eissn
0142-2782issn
1099-081Xjournal_volume
32pub_type
杂志文章,随机对照试验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::A semisolid self-emulsifying system (SES) of itraconazole consisting of oleic acid, polysorbate 80 and coajuvant (citric acid) was prepared by a hot-melt technique and then compared with hydroxypropylmethylcellulose (HPMC) solid dispersion (SD) coated onto inert sugar spheres as a reference formulation for in vitro an...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.546
更新日期:2007-05-01 00:00:00
abstract::The bioavailability of the thiazide diuretic bemetizide from a tablet containing 25 mg of this drug and 50 mg of the chemically unrelated diuretic triamterene was lower than, and significantly different (p less than 0.01) from that from a tablet containing 25 mg bemetizide alone. The mean peak plasma level of bemetizi...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章
doi:10.1002/bdd.2510030409
更新日期:1982-10-01 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::Telaprevir, a chronic hepatitis C virus (HCV) protease inhibitor, is known to be a cytochrome P450 (CYP) 3A4/5 substrate and inhibitor. In the present study, the in vitro inhibitory effect of telaprevir on the metabolism of tacrolimus in human liver microsomes was investigated using 13-O-demethyltacrolimus (M-I) as a ...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.1913
更新日期:2014-12-01 00:00:00
abstract::An equation based on the absorption potential concept was developed. This enabled us to establish an approach for the quantitative prediction of the fraction of dose absorbed. Classification of drugs into three broad categories, according to their absorption potential values in relation to the fraction of dose absorbe...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510100106
更新日期:1989-01-01 00:00:00
abstract::Infliximab (IFX) is used as a therapeutic agent for ulcerative colitis (UC) and Crohn's disease (CD). Although the dosage regimen has been established through clinical trial experience, it has yet to be assessed with a pharmacokinetic and pharmacodynamic model. The present study analysed sequential changes of clinical...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2198
更新日期:2019-07-01 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 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 gem...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2001
更新日期:2016-07-01 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::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
abstract::The influence of dose volume on drug absorption following oral administration of a highly and a poorly water soluble drug was examined in male Sprague-Dawley rats. A constant mass of each 14C-labeled compound was given via gavage in dose volumes of 1, 5, 10, and 20 mL kg-1. Blood levels, as well as the quantitative ex...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510150508
更新日期:1994-07-01 00:00:00
abstract::The pharmacokinetics of 3-(decyldimethylsilyl)-N-[2-(4-methylphenyl)-1-phenylethyl]propanamide (DMPP), an inhibitor of acyl-CoA:cholesterol acyltransferase, have been studied in the dog and the rat using 14C and 3H dual-labelled drug. In both species, gastrointestinal absorption of DMPP was slow and incomplete, amount...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510080504
更新日期:1987-09-01 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::The usefulness of a limited sampling method (LSM) to determine the bioequivalence of highly variable drugs with long half-lives was investigated. The LSM uses multiple linear regression of observed drug plasma concentrations versus area under the curve (AUC) or C(max) (peak plasma concentration) to obtain a best set o...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.275
更新日期:2001-07-01 00:00:00
abstract::The objective was to develop a population pharmacokinetic-pharmacodynamic model of caffeine's psychomotor effects in healthy, non-habitual users of caffeine. Twenty Chinese males each received a single dose of 250 mg of caffeine orally. Plasma concentrations of caffeine were determined at various times within 24 h aft...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章
doi:10.1002/bdd.714
更新日期:2010-07-01 00:00:00
abstract::A physiologic model to describe bupivacaine uptake by and elimination from brain and heart was developed. Preliminary validation of the model was accomplished by comparing concentration data predicted by the model with those determined in rabbits. The model was modified to examine similarities and differences followin...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510070204
更新日期:1986-03-01 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::The bioavailability of orally administered therapies are often significantly limited in the human intestine by the metabolic activities of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Predicting whether candidate compounds induce CYP3A4 and P-gp is a crucial stage in the drug development process, as drug-dr...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.1927
更新日期:2015-04-01 00:00:00
abstract::Sulfotransferase (SULT) 1A1 and SULT1A3 play important roles in the presystemic inactivation of beta(2) agonists in the liver and intestine, respectively. The study aimed to investigate the inhibitory effects of grapefruit juice, orange juice, green tea, black tea and oolong tea and their constituents on the activitie...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.579
更新日期:2007-12-01 00:00:00
abstract::We present a novel method for performing pharmacokinetic and metabolism studies on macromolecules that offers advantages over the existing techniques of radiolabeling, immunoassay or bioassays. Our strategy uses macromolecules with stable isotopes uniformly distributed throughout the structure. The stable isotope enri...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/(sici)1099-081x(199810)19:7<439::aid-bdd12
更新日期:1998-10-01 00:00:00
abstract::Guanfacine is used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), metabolite profiling of guanfacine was performed in plasma and urine collected from healthy Japanese adults following repeated oral administration of guanfacine exte...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2201
更新日期:2019-09-01 00:00:00
abstract::The pharmacokinetics of mexiletine and its metabolite hydroxy-methyl-mexiletine have been investigated following single-dose and during multiple-dose administration of a sustained-release form of mexiletine to six post-myocardial infarct patients. Comparison of single-dose and washout pharmacokinetics, after short-ter...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510130702
更新日期:1992-10-01 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 first day test dose versus steady-state relationship for predicting drug doses was evaluated for the situation where metabolites are produced. An organ clearance model incorporated into a digital computer program simulated drug and metabolite disposition. When the terminal elimination rate for metabolite was simil...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510040105
更新日期:1983-01-01 00:00:00
abstract::Crystalline solid dispersion of lurasidone hydrochloride (LH) was made with various polar and non-polar small molecules to overcome the poor aqueous solubility issue. LH-Glutathione (GSH) solid dispersion in 1:1 ratio was prepared by co-grinding method and characterized by using differential scanning calorimetry (DSC)...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2252
更新日期:2020-11-01 00:00:00
abstract::The bioequivalence of three oral forms of nifedipine was assessed in a triple crossover study on 12 healthy volunteers. Single 10 mg dose was given and ten blood samples were drawn during the first 8 h after administration. Highly sensitive gas chromatographic method was used for the nifedipine assay. Pharmacokinetic ...
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.2510080104
更新日期:1987-01-01 00:00:00
abstract::When drug-protein binding data are evaluated thermodynamically standard free energy (delta G0), standard enthalpy (delta H0) and standard entropy (delta S0) are usually estimated from association constants (Ka) derived from binding data obtained at only two temperatures. Estimation of delta H0 involves the assumption ...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510020304
更新日期:1981-07-01 00:00:00
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::Asialofetuin-labelled liposomes (AF-liposomes) having mean diameters of 0.13 micron ([S]) and 0.35 micron ([L]) were obtained by the subsequent extrusion method in combination with dialysis. Intravenously administered AF-liposomes [S] were rapidly cleared from the systemic circulation. By pre- and post-treatment of th...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510080404
更新日期:1987-07-01 00:00:00