Search results for "PHARMACOKINETICS"
showing 10 items of 458 documents
Nanosuspension Formulations for Low-Soluble Drugs: Pharmacokinetic Evaluation Using Spironolactone as Model Compound
2005
Various particle sizes of spironolactone as a model low solubility drug were formulated to yield micro-and nanosuspensions of the type solid lipid nanoparticles and DissoCubes. Seven oral and one i.v. formulations were tested in an in vivo pharmacokinetic study in rats with the aim of characterizing the bioavailability of spironolactone on the basis of its metabolites canrenone and 7-alpha-thiomethylspirolactone. In addition, a dose escalation study was carried out using nonmicronized spironolactone suspension as well as a nanosuspension type DissoCubes. On the basis of AUC as well as Cmax ratios, three groups of formulations were distinguished. The biggest improvement was seen with a solid…
IVIVC in oral absorption for fenofibrate immediate release tablets using a dissolution/permeation system.
2009
ABSTRACT: The usefulness of a dissolution/permeation (D/P) system to predict the in vivo performance of solid dosage forms containing the poorly soluble drug, fenofibrate, was studied. Biorelevant dissolution media simulating the fasted and fed state conditions of the human gastrointestinal tract were used in order to simulate the effect of food on the absorption of fenofibrate. Moreover, the results obtained from the D/P system were correlated with pharmacokinetic parameters obtained following in vivo studies in rats. The in vitro parameter (amount permeated in the D/P system) reflected well the in vivo performance in rats in terms of AUC and C max of fenofibric acid. This study thus demon…
Assessment and modulation of acamprosate intestinal absorption: comparative studies using in situ, in vitro (CACO-2 cell monolayers) and in vivo mode…
2003
The purpose of this study was to explore the intestinal absorption mechanism of acamprosate and to attempt to improve the bioavailability (BA) of the drug through modulation of its intestinal absorption using two enhancers (polysorbate 80 and sodium caprate) based on in situ, in vitro and in vivo models and comparing the results obtained. Intestinal transport of the drug, in the absence and in presence of polysorbate 80 (0.06, 0.28 and 9.6 mM) or sodium caprate (13 and 16 mM) was measured by using an in situ rat gut technique and Caco-2 cell monolayers. Additionally, the effect of sodium caprate on drug oral bioavailability, measured as urinary recovery, was quantified by performing in vivo…
Effect of serum protein binding on pharmacokinetics and anticoagulant activity of phenprocoumon in rats.
1980
The relationship among serum protein binding, kinetics of elimination, distribution, and anticoagulant activity of phenprocoumon was investigated in 25 selected outbred Sprague-Dawley rats which differed in the extent of serum protein binding of this drug. In addition, the serum protein binding of phenprocoumon was altered in inbred Lewis rats by continuous treatment with tolbutamide. This drug was found to displace phenprocoumon from serum proteins without affecting its intrinsic clearance. The serum free fraction values (fs)of the selected Sprague-Dawley rats ranged from 0.0053 to 0.0145. There were positive and linear correlations between fsand the first-order elimination rate constant (…
Measurement of Duloxetine in Blood Using High-performance Liquid Chromatography with Spectrophotometric Detection and Column Switching
2007
A method using high-performance liquid chromatography (HPLC) with column switching and ultraviolet (UV) spectroscopy was developed for the determination of duloxetine in human plasma. After centrifugation and addition of venlafaxine as internal standard, plasma samples were injected into the HPLC system and precleaned on a column (10 x 4.0 mm) filled with cyanopropyl (CN)-modified silica of 20 microm particle size, with use of 8% (vol/vol) acetonitrile in deionized water as eluent. Duloxetine was eluted and separated on a LiChrospher 100 CN (5-microm particle size; column size, 250 x 4.6 mm I.D.) using acetonitrile-water-potassium dihydrogenphosphate trihydrate buffer (pH, 6.4; 50:50 vol/vo…
Inhalation pharmacokinetics based on gas uptake studies. IV. The endogenous production of volatile compounds.
1983
A pharmacokinetic description of production, distribution and metabolism of endogenous volatile compounds is presented. This description uses the "gas uptake model" of a closed recirculated atmosphere in which experimental animals are exposed. As an example, the production rates of acetone, under different conditions of stimulation by xenobiotics, are calculated from published experimental data. The theoretical descriptions may serve as a basis for treating the problem of hydrocarbon exhalation in toxicological experiments with compounds eliciting lipid peroxidation.
Analgesic and thermic effects, and cerebrospinal fluid and plasma pharmacokinetics, of intracerebroventricularly administered morphine in normal and …
1998
Abstract The relationship between asthma and opioids has barely been investigated. This study examines whether active sensitization of rats changes the analgesic and thermic effects of intracerebroventricular morphine or the pharmacokinetics of the drug. Morphine (5, 10 and 20 μg) was given intracerebroventricularly to sensitized (active immunization to ovalbumin and Al(OH)3 then airway challenge with ovalbumin after 12 days) and normal (i.e. non-sensitized) male Sprague-Dawley rats. The tail-flick latencies and changes in colon temperature were determined before morphine injection and at 30 min intervals for a period of 300 min afterwards. Results were expressed as the area under the time-…
Anticancer oral therapy: Emerging related issues
2010
The use of oral anticancer drugs has shown a steady increase. Most patients prefer anticancer oral therapy to intravenous treatment primarily for the convenience of a home-based therapy, although they require that the efficacy of oral therapy must be equivalent and toxicity not superior than those expected with the intravenous treatment. A better patient compliance, drug tolerability, convenience and possible better efficacy for oral therapy as compared to intravenous emerge as the major reasons to use oral anticancer agents among oncologists. Inter- and intra-individual pharmacokinetic variations in the bioavailability of oral anticancer drugs may be more relevant than for intravenous agen…
Effect of controlled-release delivery on the pharmacokinetics of oxybutynin at different dosages: severity-dependent treatment of the overactive blad…
2004
OBJECTIVE To assess the pharmacokinetics of a controlled-release formulation of oxybutynin (OROS®-O, ALZA Corp., Mountain View, CA) at different dosages, compared with immediate-release oxybutynin (IR-O), and to determine the pharmacodynamic properties in the severity-dependent reduction of urge urinary incontinence (UUI). PATIENTS AND METHODS In all, 105 patients were enrolled in this multicentre, randomized, double-blind study. Individual dose titration was used to assess the minimum effective, maximum tolerated or maximum allowed dose of either OROS-O or IR-O. Blood samples were collected during maintenance therapy with frequent sampling to analyse for R-oxybutynin and R-desethyloxybutyn…
Poly(hydroxyethylaspartamide) derivatives as colloidal drug carrier systems
2003
Abstract Poly(hydroxyethylaspartamide) (PHEA) derivatives bearing at the polyaminoacidic backbone poly(ethyleneglycol) (2000 or 5000 Da) or both poly(ethyleneglycol) and hexadecylalkylamine as pendant moieties were investigated as polymeric colloidal drug carriers. The ability of the PHEA derivatives to solubilize hydrophobic drugs was investigated using paclitaxel, amphotericin B and methotrexate. The results demonstrated that the drug solubility depends on both macromolecule composition and drug physicochemical properties. In particular, PEG/hexadecylalkylamine co-grafting increased significantly the solubilization properties of PHEA for the considered drugs while the conjugation of PEG o…