Abstract:
:The antimalarial drug, halofantrine, is chiral and is administered clinically as the racemate. In order to define the pharmacokinetic properties of halofantrine enantiomers in the rat, male Sprague-Dawley rats (264-311 g) were given halofantrine HCl orally (n = 5; 14 mg/kg) or intravenously (i.v.) (n = 5; 2 mg/kg). Plasma samples were collected over a 72 h period, and these were assayed for halofantrine enantiomer concentrations using a stereospecific reverse phase HPLC assay. After dosing by both routes of administration the (+) enantiomer was found to have significantly higher AUC, and higher Cmax after oral dosing. Pharmacokinetic analysis indicated that in the rat, the (+) enantiomer is cleared slower, and is less extensively distributed than its antipode. The bioavailability of the enantiomers after oral administration was less than 27%. Urinary excretion was a negligible route of elimination of unchanged drug. Using allometry, the pharmacokinetics of (+/-)-halofantrine in rats scaled nicely with literature data from dogs and humans. The pharmacokinetic properties of halofantrine enantiomers in the rat resembled those seen in humans, indicating that the rat is a good model for the study of halofantrine pharmacokinetics.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
Brocks DR,Toni JWdoi
10.1002/(sici)1099-081x(199904)20:3<165::aid-bdd17keywords:
subject
Has Abstractpub_date
1999-04-01 00:00:00pages
165-9issue
3eissn
0142-2782issn
1099-081Xpii
10.1002/(SICI)1099-081X(199904)20:3<165::AID-BDD17journal_volume
20pub_type
杂志文章abstract::The effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of azosemide were evaluated using rabbit as the animal model. Each rabbit received a 4h constant intravenous infusion of 1 mg kg-1 azosemide with 0% replacement (treatment...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/(sici)1099-081x(199710)18:7<595::aid-bdd44
更新日期:1997-10-01 00:00:00
abstract::Regional pharmacokinetics is the study of the drug concentrations in specific regions of the body. It allows greater insight into the mechanisms of drug disposition than the study of systemic blood concentrations. Experimental methods in regional pharmacokinetics and their applications and limitations are reviewed. Po...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章,评审
doi:10.1002/bdd.2510110902
更新日期:1990-12-01 00:00:00
abstract::A chiral gas chromatographic assay previously developed for quantitative analysis of ethosuximide and its major metabolites in rat urine has been adapted for the analysis of the drug in plasma. Ethosuximide, both as a racemic mixture and as the individual enantiomers, was administered to conscious rats by the intraven...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.266
更新日期:2001-03-01 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::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 intestinal absorptive characteristics and the efflux mechanisms of candesartan (CDS), a novel angiotensin II type 1 receptor blocker, were investigated. The Caco-2 cells were used as models of the intestinal mucosa to assess uptake and transport of CDS. The determination of CDS was performed by HPLC-Flu. In the Ca...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.664
更新日期:2009-07-01 00:00:00
abstract:OBJECTIVE:To investigate the pharmacokinetics of budesonide and formoterol administered concomitantly in healthy adults. METHODS:Three single-dose, open-label crossover studies (n=28 each) were conducted (Study I: budesonide pMDI, formoterol DPI, budesonide pMDI+formoterol DPI; Study II: budesonide/formoterol pMDI, bu...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章,随机对照试验
doi:10.1002/bdd.622
更新日期:2008-10-01 00:00:00
abstract::The pharmacokinetics of the cardioselective beta-adrenoreceptor blocking agent atenolol have been determined following intravenous and oral dosing to the dog. After intravenous administration at 200 mg the blood levels of parent drug were found to decay tri-exponentially with a final elimination phase half-life of abo...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510040306
更新日期:1983-07-01 00:00:00
abstract::The effect of the concomitant administration of the antifungal drugs ketoconazole (KTC) and itraconazole (ITC) on the pharmacokinetics of ciprofloxacin (CIP) following short- and long-term administration in mice was investigated. Animals received either a dose of CIP (20 mg/kg, i.p.), CIP (20 mg/kg, i.p.) together wit...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.586
更新日期:2008-01-01 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::The plasma levels and tissue penetration of pefloxacin were studied after prophylactic administration to patients undergoing elective biliary surgery. Pefloxacin was administered as a single dose of 800 mg given intravenously as an infusion 1 h before surgery. Over a period of two years, cultures of bile and stone wer...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.321
更新日期:2002-10-01 00:00:00
abstract::Flow microcalorimetry was used to estimate primary binding constants for drug-albumin interactions. Measurements of heat of reaction at two temperatures illustrated the danger of extrapolation for pharmacokinetic purposes of measurements made at temperatures other than 37 degrees. The method could be used to predict c...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510050403
更新日期:1984-10-01 00:00:00
abstract::Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice-daily (b.i.d.). Raltegravir 1200 mg once-daily (q.d.) (investigational q.d. formulation of 2 × 600 mg tablets; q.d. RAL) was found to be generally well tolerated and non-inferior to th...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章,随机对照试验
doi:10.1002/bdd.2043
更新日期:2016-12-01 00:00:00
abstract::Zopiclone is a new sedative showing a rapid onset of hypnotic effect and a relatively short duration of action. The goal of this study was to assess the kinetic parameters of zopiclone and its interaction with trimipramine when administered concomitantly. Ten normal subjects each received doses of zopiclone (7.5 mg), ...
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.2510050205
更新日期:1984-04-01 00:00:00
abstract::The pharmacokinetics of a new selective oestrogen receptor modulator levormeloxifene was investigated in mice, rats, cynomolgus monkeys and humans by compartmental pharmacokinetics. Levormeloxifene was administered as an oral solution in all studies. Allometric scaling was used to predict human pharmacokinetic paramet...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.344
更新日期:2003-04-01 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::Four experimental controlled-release oral solid dosage formulations were developed and the in vitro dissolution characteristics of theophylline from these formulations were studied in USP apparatus I. Pharmacokinetic evaluation of these formulations was carried out in eight beagle dogs under fasting conditions. Theoph...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/(SICI)1099-081X(199604)17:3<259::AID-BDD95
更新日期:1996-04-01 00:00:00
abstract::The study sought to investigate the effect of genetic variants of OCT1 (OCT1-P283L and -P341L) and OCT2 (OCT2-T199I, -T201M and -A270S), which were identified in a Korean population, on the transport of lamivudine in vitro and to compare the substrate dependent effects of OCT1 and OCT2 variants with 1-methyl-4-phenylp...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.1783
更新日期:2012-04-01 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 effects of gender on the pharmacokinetics of verapamil and its active metabolite, norverapamil, following single oral dose (80 mg, Isoptin) to 12 healthy male (mean age: 25.75+/-2.42 years, mean body weight: 70.59+/-9.94 kg) and 12 healthy female subjects (mean age: 24.08+/-2.84 years, mean body weight: 56.67+/-5....
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章
doi:10.1002/bdd.512
更新日期:2006-10-01 00:00:00
abstract::Data from sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium are fitted simultaneously using NONMEM and the general linear model, ADVAN 5. Absorption and disposition parameters, serum levels, and absorption profiles were determined. The in vivo absorption profi...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/(sici)1099-081x(199804)19:3<169::aid-bdd83
更新日期:1998-04-01 00:00:00
abstract::A new sustained release dosage form of valproic acid (VPA) was developed. The new sustained release dosage form was administered (twice, with and without food) to five dogs in comparison to a standard tablet (Depakine, Labaz) and an i.v. preparation of the drug. Drug level monitoring in the plasma was performed by a G...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510050102
更新日期:1984-01-01 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::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::The oral pharmacokinetics (concentration-time profile) of four proprietary compounds in humans were predicted using the C(vss)-MRT method. The first step was to demonstrate superposition of intravenous (i.v.) pharmacokinetic profiles of preclinical species following mathematical transformation of their respective conc...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.632
更新日期:2008-11-01 00:00:00
abstract::In order to determine the absolute bioavailability, both oral and intravenous administrations of a drug are often used. Recently a new method has been proposed to determine absolute bioavailability in the absence of intravenous dose. Following a single oral dose, this method requires oral and renal clearance data from...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/(sici)1099-081x(199708)18:6<465::aid-bdd41
更新日期:1997-08-01 00:00:00
abstract::Sildenafil is the first oral therapeutic agent for the management of male erectile dysfunction. Its oral bioavailability is only 40% due to extensive presystemic elimination, mainly by CYP3A4. This study examined the effect of coadministration of ciprofloxacin or clarithromycin, which inhibit CYP3A4, on the bioavailab...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.488
更新日期:2006-03-01 00:00:00
abstract::Twenty-four healthy volunteers, aged 21-59 years, received single 30 mg oral doses of the benzodiazepine hypnotic temazepam. Levels of intact temazepam were determined in multiple plasma samples drawn during 48 h after dosage. Intact temazepam, its direct glucuronide conjugate, and the conjugate of its demethylated (o...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510110604
更新日期:1990-08-01 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 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