Pharmacokinetics of ketoconazole administered intravenously to dogs and orally as tablet and solution to humans and dogs.

Abstract:

:The single-dose pharmacokinetics and bioavailability of three ketoconazole formulations were evaluated using HPLC in five healthy human volunteers and six male mongrel dogs. The human volunteers received 400 mg po of ketoconazole as tablet (Ktab) and solution (Ksol) formulations. The dogs received 400 mg po of Ktab and Ksol, and 376 mg iv of an intravenous dose (Kiv). In humans the AUC value for Ksol (62.21 +/- 21.2 microgram X h/ml; mean +/- SD) was significantly greater than for Ktab (50.0 +/- 15.2 micrograms X h/ml; p less than 0.05). Peak serum concentrations (Cmax), time to peak serum concentrations (tmax), t1/2, and the terminal elimination rate constant (kel) did not differ between Ktab and Ksol. This suggests that the administration of Ksol may be a useful alternative to dosage increases in situations where low bioavailability of ketoconazole in tablet form is suspected. The mean systemic clearance (CLs) of Kiv in dogs was 2.74 +/- 1.10 mL/min/kg, the volume of distribution at steady state (Vdss) was 0.72 +/- 0.28 L/kg, and the half-life was 2.7 +/- 1.6 h. Considerable variability was seen in the AUC of ketoconazole, particularly with the oral preparations. The absolute bioavailability of Ktab was 0.50 +/- 0.38, which did not differ statistically from that of Ksol, 0.56 +/- 0.23. The Ksol showed less variability in AUC, Cmax, and F values than did Ktab, and two dogs with low bioavailability with Ktab (0.04 and 0.07) had substantially greater bioavailability with Ksol (F = 0.96 and 0.57, respectively). Evaluation of Kiv in dogs confirms decreased bioavailability from orally administered tablet formulations of ketoconazole.

journal_name

J Pharm Sci

authors

Baxter JG,Brass C,Schentag JJ,Slaughter RL

doi

10.1002/jps.2600750504

subject

Has Abstract

pub_date

1986-05-01 00:00:00

pages

443-7

issue

5

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)47101-1

journal_volume

75

pub_type

杂志文章
  • Novel Insights to Enhance Therapeutics With Acyclovir in the Management of Herpes Simplex Encephalitis.

    abstract::Acyclovir is an antiviral drug poorly absorbed in the gastrointestinal tract due to its hydrophilicity, with low oral bioavailability (~20%). Although acyclovir is prescribed in the management of herpes simplex encephalitis (HSE), the disease has a poor prognosis, particularly if the treatment is delayed, reaching mor...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.xphs.2021.01.003

    authors: Gurgel Assis MS,Fernandes Pedrosa TC,de Moraes FS,Caldeira TG,Pereira GR,de Souza J,Ruela ALM

    更新日期:2021-01-13 00:00:00

  • The developability classification system: application of biopharmaceutics concepts to formulation development.

    abstract::A revised classification system for oral drugs was developed using the biopharmaceutics classification system (BCS) as a starting point. The revised system is designed to have a greater focus on drug developability. Intestinal solubility, the compensatory nature of solubility and permeability in the small intestine an...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22217

    authors: Butler JM,Dressman JB

    更新日期:2010-12-01 00:00:00

  • Expression of Carboxylesterase Isozymes and Their Role in the Behavior of a Fexofenadine Prodrug in Rat Skin.

    abstract::The expression of carboxylesterase (CES) and the transdermal movement of an ester prodrug were studied in rat skin. Ethyl-fexofenadine (ethyl-FXD) was used as a model lipophilic prodrug that is slowly hydrolyzed to its parent drug, FXD (MW 502). Among the CES1 and CES2 isozymes, Hydrolase A is predominant in rat skin ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.24648

    authors: Imai T,Ariyoshi S,Ohura K,Sawada T,Nakada Y

    更新日期:2016-02-01 00:00:00

  • Solubility advantage of amorphous pharmaceuticals, part 3: Is maximum solubility advantage experimentally attainable and sustainable?

    abstract::A method is described for screening compounds that inhibit crystallization in solution to enable more accurate measurement of amorphous drug solubility. Three polymers [polyvinylpyrrolidone, hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose acetate succinate (HPMCAS)] were screened for their ability to ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22643

    authors: Murdande SB,Pikal MJ,Shanker RM,Bogner RH

    更新日期:2011-10-01 00:00:00

  • Peptide derivation of poorly absorbable drug allows intestinal absorption via peptide transporter.

    abstract::The purpose of the present study was to examine whether the intestinal absorption of low-permeability drugs could be improved by utilization of the intestinal influx transporter PEPT1. We investigated whether peptide derivatives of poorly absorbable nonamino acid-like drugs might be substrates of PEPT1, using rebamipi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21551

    authors: Kikuchi A,Tomoyasu T,Tanaka M,Kanamitsu K,Sasabe H,Maeda T,Odomi M,Tamai I

    更新日期:2009-05-01 00:00:00

  • Straight-chain naltrexone ester prodrugs: diffusion and concurrent esterase biotransformation in human skin.

    abstract::Naltrexone (NTX) is an opioid antagonist used for treatment of narcotic dependence and alcoholism. Transdermal naltrexone delivery is desirable to help improve patient compliance. The purpose of this study was to increase the delivery rate of NTX across human skin by using lipophilic alkyl ester prodrugs. Straight-cha...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.10239

    authors: Stinchcomb AL,Swaan PW,Ekabo O,Harris KK,Browe J,Hammell DC,Cooperman TA,Pearsall M

    更新日期:2002-12-01 00:00:00

  • Lyophilization Process Design and Development: A Single-Step Drying Approach.

    abstract::High-throughput lyophilization process was designed and developed for protein formulations using a single-step drying approach at a shelf temperature (Ts) of ≥40°C. Model proteins were evaluated at different protein concentrations in amorphous-only and amorphous-crystalline formulations. Single-step drying resulted in...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2018.11.021

    authors: Pansare SK,Patel SM

    更新日期:2019-04-01 00:00:00

  • Utilising Magnetically Isolated Lysosomes for Direct Quantification of Intralysosomal Drug Concentrations by LC-MS/MS Analysis: An Investigatory Study With Imipramine.

    abstract::Lysosomes are acidic intracellular organelles that can extensively sequester basic lipophilic drugs due to pH and membrane partitioning, and therefore may significantly influence subcellular drug concentrations. Current in vitro methods for lysosomal drug sequestration evaluation typically lack the ability to accurate...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2020.05.026

    authors: Francis L,Harrell A,Hallifax D,Galetin A

    更新日期:2020-09-01 00:00:00

  • Synthesis of N,N'-bis(3-substituted benzylideneaminopropyl)-piperazines and their anti-inflammatory, antiproteolytic, and anticonvulsant properties.

    abstract::Some N,N'-bis(3-substituted benzylideneaminopropyl) piperazines were synthesized and characterized by their sharp melting points and elemental analyses. These substituted piperazines possessed anti-inflammatory activity, and the protection afforded by these compounds against carrageenan-induced edema ranged from 23 to...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600650323

    authors: Chaturvedi AK,Sastry BV,Chaudhari A,Parmar SS

    更新日期:1976-03-01 00:00:00

  • Identification of Endogenous Biomarkers to Predict the Propensity of Drug Candidates to Cause Hepatic or Renal Transporter-Mediated Drug-Drug Interactions.

    abstract::Drug transporters expressed in liver and kidney play a critical role in the elimination of a wide range of drugs and xenobiotics and inhibition of these transporters may therefore cause clinically significant drug-drug interactions (DDIs). Currently, in vitro transporter inhibition data are used to assess the risk tha...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.xphs.2017.04.007

    authors: Chu X,Chan GH,Evers R

    更新日期:2017-09-01 00:00:00

  • Pair distribution function X-ray analysis explains dissolution characteristics of felodipine melt extrusion products.

    abstract::Solid solutions of felodipine with EUDRAGIT E and EUDRAGIT E/NE were shown to dramatically increase the dissolution rate of felodipine in biorelevant media. Of the two polymer systems, extrudates containing 5% EUDRAGIT NE showed a faster dissolution rate and less recrystallization (no precipitation within 2 h). Althou...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21534

    authors: Nollenberger K,Gryczke A,Meier Ch,Dressman J,Schmidt MU,Brühne S

    更新日期:2009-04-01 00:00:00

  • Progestin permeation through polymer membrane V: Progesterone release from monolithic hydrogel devices.

    abstract::Progesterone release from monolithic devices prepared from various copolymers of poly(hydroxyethyl methacrylate) and poly(methoxyethoxyethyl methacrylate) or poly(methoxyethyl methacrylate) was examined. In general, plots of the fraction of drug released versus (time)1/2 were linear during the early stages of drug rel...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600700226

    authors: Song SZ,Cardinal JR,Kim SH,Kim SW

    更新日期:1981-02-01 00:00:00

  • Aerosol Inhalation Delivery of Triazavirin in Mice: Outlooks for Advanced Therapy Against Novel Viral Infections.

    abstract::Under pandemic-caused emergency, evaluation of the potential of existing antiviral drugs for the treatment of COVID-19 is relevant. Triazavirin, an antiviral drug developed in Russia for per-oral administration, is involved in clinical trials against SARS-CoV-2 coronavirus. This virus has affinity to epithelial cells ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2020.11.016

    authors: Valiulin SV,Onischuk AA,Dubtsov SN,Baklanov AM,An'kov SV,Plokhotnichenko ME,Tolstikova TG,Dultseva GG,Rusinov VL,Charushin VN,Fomin VM

    更新日期:2020-11-26 00:00:00

  • Immunohistochemical localization of insulin-degrading enzyme along the rat intestine, in the human colon adenocarcinoma cell line (Caco-2), and in human ileum.

    abstract::Insulin-degrading enzyme (IDE) has been implicated in the intracellular degradation of insulin in insulin target cells. Knowledge of the existence of this enzyme in the intestine will be beneficial to the achievement of clinical oral efficacy of insulin. A comparative study was conducted with rat intestine, human colo...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js960035q

    authors: Chang LL,Stout LE,Wong WD,Buls JG,Rothenberger DA,Shier WT,Sorenson RL,Bai JP

    更新日期:1997-01-01 00:00:00

  • A novel off-center paddle impeller (OPI) dissolution testing system for reproducible dissolution testing of solid dosage forms.

    abstract::Dissolution testing is routinely conducted in the pharmaceutical industry to provide in vitro drug release information for quality control purposes. The most common dissolution testing system for solid dosage forms is the United States Pharmacopeia (USP) Dissolution Testing Apparatus 2. This apparatus is very sensitiv...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22783

    authors: Wang Y,Armenante PM

    更新日期:2012-02-01 00:00:00

  • Validation of washing procedures for maintaining a microbiologically clean gel filtration column.

    abstract::Chromatographic gel filtration matrixes used in various separation techniques are subject to microbial contamination. The need for a microbe-free column is critical when preparing materials that require a low or zero microbial count. This report proposes two alternative washing systems: 0.02 N HCl containing 0.81% NaC...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600690205

    authors: Wen LF,Bohannon T,Crabb A,Mamaril F

    更新日期:1980-02-01 00:00:00

  • Disposition of [14C]pinacidil in humans.

    abstract::Pinacidil [(+/-)-2-cyano-1-(4-pyridyl)-3-(1,2,2-trimethylpropyl)guanidine monohydrate] is a novel, direct-acting vasodilator antihypertensive agent. The cyano 14C-labeled drug is rapidly and completely absorbed after an oral 12.5-mg dose in solution. The blood:plasma concentration ratios (0.8-0.9) indicate transient p...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600770212

    authors: DeLong AF,Oldham SW,DeSante KA,Nell G,Henry DP

    更新日期:1988-02-01 00:00:00

  • Synthesis, stability, and pharmacological evaluation of nipecotic acid prodrugs.

    abstract::Nipecotic acid (1), one of the most potent in vitro inhibitors of neuronal and glial gamma-amino butyric acid (GABA) uptake, is inactive as an anticonvulsant when administered systemically. To obtain in vivo active prodrugs of (1), we synthesized four new nipecotic acid esters (3-6), which were obtained by chemical co...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js980302n

    authors: Bonina FP,Arenare L,Palagiano F,Saija A,Nava F,Trombetta D,de Caprariis P

    更新日期:1999-05-01 00:00:00

  • Physico-chemical and technological properties of sodium naproxen granules prepared in a high-shear mixer-granulator.

    abstract::In the present work, authors produced tablets of anhydrous sodium naproxen by wet granulation using a high-shear mixer-granulator. Drug hydrated to the tetrahydrated form, as observed by X-ray powder diffractometry. After wet granulation, authors then performed two different drying procedures, obtaining granules of di...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21400

    authors: Di Martino P,Malaj L,Censi R,Martelli S

    更新日期:2008-12-01 00:00:00

  • Monitoring the film coating unit operation and predicting drug dissolution using terahertz pulsed imaging.

    abstract::Understanding the coating unit operation is imperative to improve product quality and reduce output risks for coated solid dosage forms. Three batches of sustained-release tablets coated with the same process parameters (pan speed, spray rate, etc.) were subjected to terahertz pulsed imaging (TPI) analysis followed by...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21766

    authors: Ho L,Müller R,Gordon KC,Kleinebudde P,Pepper M,Rades T,Shen Y,Taday PF,Zeitler JA

    更新日期:2009-12-01 00:00:00

  • Effect of micellization on rate of cupric-ion-promoted hydrolysis of dicarboxylic acid hemiesters.

    abstract::The effect of micellar sodium lauryl sulfate on the rate of cupric-ion-promoted hydrolysis of some dicarboxylic acid hemiesters was investigated at pH 5, ionic strength 0.1 M, and 40, 45, and 50 degrees. The rate of cupric-ion-promoted hydrolysis of sodium n-decyloxalate in the micellar phase is about 50 times as fast...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600651206

    authors: Ong JT,Kostenbauder HB

    更新日期:1976-12-01 00:00:00

  • Assay and disposition of carvedilol enantiomers in humans and monkeys: evidence of stereoselective presystemic metabolism.

    abstract::Carvedilol is a new beta-blocking agent with vasodilating activities, which is a racemic mixture of R(+)- and S(-)-enantiomers. Since the two enantiomers differ in pharmacological properties, it is necessary to individually measure their plasma concentrations in order to evaluate the pharmacological effects of racemic...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600790704

    authors: Fujimaki M,Murakoshi Y,Hakusui H

    更新日期:1990-07-01 00:00:00

  • Dissolution profiles for finely divided drug suspensions.

    abstract::A suspension of micronized prednisolone acetate was separated into four fractions by the technique of centrifugal elutriation. Data showed that each fraction had a narrow particle size. The dissolution experiments were carried out under sink conditions (less than 10% of saturation concentration) in a dissolution appar...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600720225

    authors: Mauger JW,Howard SA,Amin K

    更新日期:1983-02-01 00:00:00

  • Synthesis and biological evaluation of p-bromospiperone as potential neuroleptic drug.

    abstract::p-Bromospiperone was prepared from the reaction of spiperone with bromine. It was tested for dopamine receptor binding affinity in vitro and its ability to stimulate prolactin secretion in vivo. The results indicate no significant change of biological activities due to the bromination of spiperone. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600690835

    authors: Huang CC,Friedman AM,So R,Simonovic M,Meltzer HY

    更新日期:1980-08-01 00:00:00

  • Stable isotope coadministration methodology for the estimation of the fraction of imipramine metabolized to desipramine.

    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...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600790203

    authors: Sasaki Y,Shinohara Y,Baba S

    更新日期:1990-02-01 00:00:00

  • Probing the Tryptophan Environment in Therapeutic Proteins: Implications for Higher Order Structure on Tryptophan Oxidation.

    abstract::Tryptophan (Trp) oxidation in proteins leads to a number of events, including changes in color, higher order structure (HOS), and biological activity. We describe here a number of new findings through a comprehensive characterization of 6 monoclonal antibodies (mAbs) following selective oxidation of Trp residues by 2,...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2018.12.027

    authors: Barnett GV,Balakrishnan G,Chennamsetty N,Hoffman L,Bongers J,Tao L,Huang Y,Slaney T,Das TK,Leone A,Kar SR

    更新日期:2019-06-01 00:00:00

  • Potential thyroliberin affinity labels II: Chloroacetyl substituted phenylalanyl prolineamides.

    abstract::Three analogs of thyroliberin (I) were prepared. These compounds, N-m-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIa), N-p-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIb) and N-chloroacetyl-alanyl-phenylalanyl-prolineamide (IX), were designed as potential I antagonist affinity labels. However, no significant a...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600710928

    authors: Goebel RJ,Currie BL,Bowers CY

    更新日期:1982-09-01 00:00:00

  • Absorption and bioavailability of glucosamine in the rat.

    abstract::The objective of this study was to determine reasons behind the low oral (p.o.) bioavailability of glucosamine. By using male Sprague-Dawley rats, the movement of glucosamine through everted gut, the effect of dose and glucose, and inhibition of a glucose transporter (GLUT2) by quercetin were studied. Glucosamine phar...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23145

    authors: Ibrahim A,Gilzad-kohan MH,Aghazadeh-Habashi A,Jamali F

    更新日期:2012-07-01 00:00:00

  • Fluorometric determination of trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles in biological materials.

    abstract::Interest in the 5-, 6-, and 7-trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles as potent, orally active anti-inflammatory agents required a method for their determination in serum, urine, and feces to permit studies of their absorption, metabolism, and excretion. A simple, rapid, sensitive, and specific pro...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600651218

    authors: Kaiser DG,Liggett WF,Forist AA

    更新日期:1976-12-01 00:00:00

  • The Effects of Feed Frame Parameters and Turret Speed on Mini-Tablet Compression.

    abstract::Die filling is a critical process step during tablet production as it defines the tablet weight. Achieving die fill consistency during production of mini-tablets, tablets with diameters ≤6 mm, is considerably more challenging. Although die filling in rotary presses had been studied in relation to the feed paddle desig...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2018.09.005

    authors: Goh HP,Sia Heng PW,Liew CV

    更新日期:2019-03-01 00:00:00