Abstract：
:The pharmacokinetics of the antirheumatic proquazone and its conjugated and unconjugated m-hydroxy metabolites were investigated in five healthy male volunteers after both intravenous (75 and 122 mg) and peroral (300 and 900 mg via capsules) administration. For adequate intravenous dosing of the poorly water-soluble proquazone, advantage was taken of the high degree of protein binding of the drug. Proquazone was admixed with 40% sterile human albumin, and these proteinaceous drug-containing solutions were injected. The pharmacokinetics of proquazone and of the measured metabolites after intravenous administration and after the 300-mg po dose were first order, whereas deviations from linear kinetics were observed at the 900-mg dose level. The apparent half-lives of the alpha, beta, and gamma phases of proquazone in plasma were 2, 14, and 76 min, respectively, on intravenous administration. The total clearance of proquazone was 700 mL/min, which indicated a high hepatic extraction. The apparent volume of distribution at steady state was 40 L, implying extensive binding or partitioning of the lipophilic drug in the tissues. Unchanged proquazone (less than 0.001%), the m-hydroxy metabolite (less than 1.0%), and the conjugated m-hydroxy metabolite (20%) were renally excreted after intravenous administration. The extent of absorption of proquazone was approximately 7% and was entirely the result of a large first-pass effect. Digital computer analysis of the data after intravenous administration was performed with a linear three-compartment model. A model-independent approach was used in the analysis of the peroral data.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Hinderling PH,Roos Adoi
10.1002/jps.2600730312subject
Has Abstractpub_date
1984-03-01 00:00:00pages
332-40issue
3eissn
0022-3549issn
1520-6017pii
S0022-3549(15)46033-2journal_volume
73pub_type
杂志文章abstract：:The objective of this study was to establish the optimal blood concentrations of the potent P-glycoprotein (P-gp) inhibitor GF120918 (Elacridar) required to achieve maximal knockout of this efflux transporter in the blood-brain barrier (BBB) of mice, rats, and guinea pigs. Genetic mdr1a/b(-/-) knockout mice and "chemi...
journal_title：Journal of pharmaceutical sciences
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abstract：:Alkyl 2-imidazolyl disulfide compounds are novel antitumor agents, one of which is currently being evaluated in Phase I clinical trials. These molecules contain an unsymmetrical disulfide fragment, the lipophilic and electronic contributions of which are still not defined in the literature. Lipophilicity, ionization, ...
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journal_title：Journal of pharmaceutical sciences
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abstract：:We have previously reported the development of novel nanocapsules made of polyarginine (PArg) specifically designed for the delivery of small anticancer drugs into cells. Our goal, in this work, has been to investigate the potential of these nanocarriers for oral delivery of peptide anticancer drugs. To reach this obj...
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journal_title：Journal of pharmaceutical sciences
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abstract：:Cosalane is a potent inhibitor of HIV replication with multiple sites of action. The purposes of this study were to (a) determine the extent and nature of cosalane binding to mucin, alpha(1)-acid glycoprotein (AAG), plasma, and human (HSA) and bovine serum (BSA) albumin, and (b) determine the primary site(s) of cosala...
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.20894
更新日期：2007-09-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
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更新日期：2009-09-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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更新日期：1996-01-01 00:00:00
abstract：:Male fertility has reportedly been regulated by the long-term, continuous administration of testosterone. To deliver the testosterone at a controlled rate for a month or longer, a bandage-type, testosterone-releasing, disk-shaped device was developed. In vitro drug elution studies demonstrated that a constant release ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730811
更新日期：1984-08-01 00:00:00
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更新日期：2019-02-01 00:00:00
abstract：:The application of a stable isotope coadministration technique for estimating the fraction (fm) of imipramine (IP) that is converted to desipramine (DMI) is described. Four healthy male subjects received 25 mg of IP-d4 hydrochloride orally with 25 mg of DMI hydrochloride. The plasma concentrations of IP-d4, DMI-d4, an...
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pub_type： 杂志文章
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
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更新日期：1981-08-01 00:00:00
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更新日期：2014-09-01 00:00:00
abstract：:A novel drug-deliver device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using bovine insulin and bovine albumin as model polypeptide drugs. Equimolar mixtures of the calcium phosphate powders containing bovine insulin and bo...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600830229
更新日期：1994-02-01 00:00:00
abstract：:A crude chloroform-soluble fraction of the ethanol extract of the leaves of Bursera klugii showed activity against two test systems, the P-388 lymphocytic leukemia (3PS) and the human epidermoid carcinoma of the nasopharynx (9KB). The PS activity was due to two constituents, sapelins A and B. ...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600660645
更新日期：1977-06-01 00:00:00
abstract：:The quassinoids bruceantin, brucein D, brucein E, bruceoside A, and brusatol significantly inhibited P-388 lymphocytic leukemic cell RNA and protein synthesis in tissue culture. However, DNA synthesis inhibition seemed to correlate more directly with the anti-neoplastic activity of these compounds in the in vivo P-338...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680726
更新日期：1979-07-01 00:00:00
abstract：:Development of high-throughput release and characterization assays is critical for the effective support of the rapidly growing biologics pipeline for biotherapeutics. Clipping of polypeptide chains is commonly monitored during process optimization, formulation development, and stability studies. A reduced capillary e...
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doi：10.1002/jps.22710
更新日期：2011-12-01 00:00:00
abstract：:L-3-(3-Hydroxy-4-pivaloyloxyphenyl)alanine (1, NB-355) is a novel L-dopa prodrug. After oral administration with carbidopa in rats, 1 demonstrated 2.3 times longer duration (MRT) and 1.4 times larger bioavailability (AUC) on plasma L-dopa concentrations than those of L-dopa itself. Similar results were obtained in dog...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600780703
更新日期：1989-07-01 00:00:00
abstract：:Accurate prediction of target occupancy facilitates central nervous system drug development. In this review, we discuss the predictability of serotonin transporter (SERT) occupancy in human brain estimated from in vitro Ki values for human SERT and plasma concentrations of unbound drug (Cu,plasma), as well as the impa...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2017.05.007
更新日期：2017-09-01 00:00:00
abstract：:Corneal permeability data taken from the literature were analyzed for possible quantitative relationships with physicochemical properties. Although a parabolic relationship was obtained with good correlation between lipophilicity, as expressed by the 1-octanol-water partition coefficients, log Poctanol (or the distrib...
journal_title：Journal of pharmaceutical sciences
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更新日期：1996-08-01 00:00:00
