Abstract:
:Niosomes (non-ionic surfactant vesicles) prepared from C16G2 (a hexadecyl-diglycerol ether), and loaded with doxorubicin, were administered intraperitoneally to male AKR mice at dose levels of 0, 2.5, 5.0, and 10.0 mg kg-1. Free drug was given at 10.0 mg kg-1 by the intraperitoneal route. At a dose level of 10.0 mg kg-1, peak doxorubicin levels in the central compartment were attained faster with the free drug than with the niosome formulation. However, the peak plasma levels were similar for the free drug and the niosome preparation at the 10 mg kg-1 dose level. With doxorubicin administered as the niosome preparation by the intraperitoneal route at 2.5, 5.0, and 10.0 mg kg-1, mean peak plasma concentrations of the drug showed a tendency to be dose-related although the differences were not significant. Over the 24 h period of the experiment, with doxorubicin at 10 mg kg-1, the niosome formulation delivered significantly more drug to the plasma compartment than the free drug (p < 0.05). When doxorubicin was given in niosomes at 2.5, 5.0 and 10.0 mg kg-1 by the intraperitoneal route, the resulting levels of doxorubicin in cardiac tissue were not dose related and the differences not significant and, although the mean peak cardiac-tissue concentration was higher in animals receiving the free drug at 10.0 mg kg-1 intraperitoneally than in mice given intraperitoneal doxorubicin niosomes at this dose level, the differences were again not significant. There were clinical signs of toxicity in mice given doxorubicin-containing niosomes intraperitoneally at 5.0 and 10.0 mg kg-1, and at post-mortem an accumulation of fluid in the pleural cavity was evident. These changes were not seen in mice dosed intraperitoneally with free drug at 10 mg kg-1, or in animals given doxorubicin niosomes intraperitoneally at 2.5 mg kg-1. In mice dosed intraperitoneally with doxorubicin niosomes at 12.0 mg kg-1 and at a dose volume of 0.2-0.4 mL, histological examination of the lungs demonstrated a congestion of the alveolar capillaries, and an increased number of acute inflammatory cells in the alveolar walls. There was no histological evidence of lung toxicity in mice dosed with doxorubicin niosomes at 12.0 mg kg-1 when the formulation was administered with the higher dose volume of 1.8-2.0 mL. Importantly there was no histological evidence of lung toxicity in mice dosed with empty niosomes intraperitoneally or with doxorubicin niosomes given intravenously at 12.0 mg kg-1.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
Uchegbu IF,Turton JA,Double JA,Florence ATdoi
10.1002/bdd.2510150807subject
Has Abstractpub_date
1994-11-01 00:00:00pages
691-707issue
8eissn
0142-2782issn
1099-081Xjournal_volume
15pub_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::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::Equilibrative nucleoside transporters (ENTs) 1 and 2 reportedly accept fluorouracil as a substrate. Here, we evaluated ENT1/2 expression at the messenger RNA (mRNA), protein, and functional levels in a panel of four triple-negative breast cancer (TNBC) cell lines, BT-549, Hs578T, MDA-MB-231, and MDA-MB-435, and we exa...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2261
更新日期:2021-01-10 00:00:00
abstract::The pharmacokinetics and pharmacodynamics of furosemide were compared after an oral administration or a direct administration of Lasix into the duodenum in humans (40 mg). Furosemide was absorbed quickly after a direct administration of Lasix into the duodenum; the peak plasma concentration of furosemide was reached w...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章
doi:10.1002/(sici)1099-081x(199712)18:9<753::aid-bdd63
更新日期:1997-12-01 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::Several research groups have reported that in man the oral administration of propranolol with food leads to a marked increase (about 50 per cent) in the area under the plasma concentration-time curve (AUCpo) of this well absorbed and highly metabolized drug. An acute change in hepatic metabolic enzyme activity has bee...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510140305
更新日期:1993-04-01 00:00:00
abstract::Methotrexate (MTX) is an antifolate agent used in the treatment of numerous types of cancer, and eliminated by active tubular secretion via organic anion transporter 3 (OAT3). Gastric antisecretory drugs, such as proton pump inhibitors (PPIs) and histamine H2 receptor antagonists, are widely used among patients with c...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2091
更新日期:2017-12-01 00:00:00
abstract::The tumour uptake as well as the anti-tumour activity of RS-1541 (palmitoyl rhizoxin), a potent antineoplastic agent, were investigated in mice bearing M5076 sarcoma. After intravenous administration, 14C-RS-1541 preferentially bound to the lipoproteins, to which 14C-rhizoxin did not bind. 14C-RS-1541 showed persistin...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510150202
更新日期:1994-03-01 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 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::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::It was shown previously that the anticancerous cytotoxic oxygenated triterpenes, cucurbitacin E (Cuc E) and its deacetylated form, cucurbitacin I (Cuc I), interacted differently with human serum albumin. In this study, the biochemical stability of Cuc E was investigated in vitro by reverse-phase high performance liqui...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.673
更新日期:2009-10-01 00:00:00
abstract::The pharmacokinetics of a non-narcotic analgesic, DA-5018, were compared after single intravenous (i.v.), subcutaneous (s.c.), and oral administrations, and after multiple (seven consecutive days) s.c. administration to rats. After i.v. administration of DA-5018, 1, 2, and 5 mg kg-1, the pharmacokinetic parameters of ...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/(sici)1099-081x(199803)19:2<101::aid-bdd81
更新日期:1998-03-01 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
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journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章
doi:10.1002/bdd.594
更新日期:2008-04-01 00:00:00
abstract::The inhibition potencies of aripiprazole and its active metabolite, dehydroaripiprazole, on the activities of human multidrug resistance protein 1 (MDR1/ABCB1; P-glycoprotein), breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 4 (MRP4/ABCC4), that are drug efflux transporters ex...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.1801
更新日期:2012-09-01 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::The enantioselective pharmacokinetics of a new anxiolytic, pazinaclone (DN-2327), and its active metabolite, M-II, were studied in animals. In rats and dogs given racemic pazinaclone intravenously, the total clearance and volume of distribution of (S)-pazinaclone were lower than those of (R)-pazinaclone, whereas the o...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510160906
更新日期:1995-12-01 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::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::Oral doses of amygdalin and intraperitoneal (i.p.) doses of potassium cyanide (KCN) in the near-lethal range were administered to CD2F1 female mice. Blood cyanide levels were then measured as a function of time. The maximum cyanide level after amygdalin administration was reached at about 11/2 to 2 h and was within th...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510010409
更新日期:1980-04-01 00:00:00
abstract::The present study aimed to investigate the effect of atorvastatin on the intravenous and oral pharmacokinetics of verapamil in rats. The pharmacokinetic parameters of verapamil were measured after an oral (9 mg/kg) or intravenous (3 mg/kg) administration of verapamil to rats in the presence and absence of atorvastatin...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.582
更新日期:2008-01-01 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::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::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
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更新日期:1998-11-01 00:00:00
abstract::Sulforaphane (SFN) is an isothiocyanate that is present in widely consumed vegetables. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents. Recently it was found that SFN could also suppress the growth of intestinal polyps in the ApcMin/+ mouse. In the prese...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.522
更新日期:2006-12-01 00:00:00
abstract::EXP631, 4-(3-thienyl)-alpha, alpha,1-trimethyl-4-piperidine-methanol hemi-fumarate salt (I), is a centrally acting non-opioid analgesic compound with monoamine uptake blocking properties. EXP631 has analgesic effects in several animal models. It is intended to be used for the treatment of moderate to moderately severe...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510140608
更新日期:1993-08-01 00:00:00
abstract::Pharmacokinetics in rabbits following intravenous administration and in vitro protein binding were studied for two new salts of erythromycin (erythromycin maltobionate and erythromycin fumarate). Serum erythromycin levels following intravenous injection were described by two compartment model kinetics, and values for ...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510130606
更新日期:1992-08-01 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::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
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更新日期:2010-10-01 00:00:00