Search results for "Pharmacokinetic"
showing 10 items of 474 documents
Evidence of a specialized transport mechanism for the intestinal absorption of baclofen
1989
Absorption of the spasmolytic drug baclofen in three selected intestinal segments of living anaesthetized rats in situ, is shown to be a specialized transport mechanism obeying Michaelis-Menten kinetics. Equation parameters were calculated through different procedures, whose features are discussed. A computer method based on the integrated form of Michaelis-Menten equation which reproduces the entire time course of drug absorption from the data found in three intestinal perfusion series at different initial concentrations, yielded Vm and Km values of 12.0 mg h-1 and 8.0 mg, respectively, in the mean segment of the small intestine, a rather selective absorption site for baclofen. Lesser but …
Intrinsic Absolute Bioavailability Prediction in Rats Based on In Situ Absorption Rate Constants and/or In Vitro Partition Coefficients: 6‐Fluoroquin…
2000
A preliminary study attempting to predict the intrinsic absolute bioavailability of a group of antibacterial 6-fluoroquinolones-including true and imperfect homologues as well as heterologues-was carried out. The intrinsic absolute bioavailability of the test compounds, F, was assessed on permanently cannulated conscious rats by comparing the trapezoidal normalized areas under the plasma concentration-time curves obtained by intravenous and oral routes (n = 8-12). The high-performance liquid chromatography analytical methods used for plasma samples are described. Prediction of the absolute bioavailability of the compounds was based on their intrinsic rat gut in situ absorption rate constant…
Effects of Ethanol on Intestinal Absorption of Drugs
1999
The effect of chronic alcohol intake on the intestinal absorption of seven compounds belonging to a homologous series (ciprofloxacin derivatives) was evaluated using an in situ rat gut technique that measures the intrinsic absorption rates of the compounds both in control and chronic alcohol-fed rats. For chronic alcohol treatment, the animals were fed a liquid diet containing ethanol (36% of calories), whereas an isocaloric diet was given to the pair-fed control animals. The biophysical absorption model, relating the intestinal absorption rate constants and partition indexes of the tested compounds, was then established either for control or alcohol-fed animals. Differences were analyzed a…
Rectal pH in children
1989
In an attempt to establish normal values for rectal pH in children, we have measured pH in 100 paediatric patients. Measurement of rectal pH was performed in 25 infants and 75 children (27 girls and 73 boys) using a monocrystalline antimony electrode. Rectal pH was 9.6 +/- 0.9 (mean +/- SD, range 7.2 to 12.1) and was independent of sex, age and nutrition. This wide range of rectal pH values offers a possible explanation for the widely scattered bioavailability of drugs administered by the rectal route. Mean rectal pH was considerably higher than that reported for adults; this unexpected alkalinity should be taken into account, when drug formulations are considered for rectal administration …
Oral topotecan in children with recurrent or progressive high-grade glioma: a Phase I/II study by the German Society for Pediatric Oncology and Hemat…
2004
BACKGROUND Continuous oral treatment with topotecan may be more effective than the typical 1-day and 5-day treatment schedules. In previous studies of continuous treatment with topotecan, increased intestinal side effects were reported in adult patients; however, the experience in pediatric patients and patients with high-grade glioma is quite limited. METHODS Thirty-two pediatric patients with recurrent high-grade glioma (16 females and 16 males; median age, 9.5 years) were enrolled in the current Phase I/II study. Tumor locations included the cerebral cortex (n = 5), pons (n = 18), and other sites (n = 9). An injectable formulation of topotecan was administered orally, in ice-cold orange …
Regional perfusion and oxygenation of tumors upon methylxanthine derivative administration
1998
Abstract Purpose: The use of methylxanthine derivatives has been postulated as a means of increasing tumor perfusion and thus ameliorating tumor hypoxia. The aim of this study was to quantify and compare the effects of three methylxanthine derivatives: pentoxifylline (PX), torbafylline (TB), and HWA 138 (HW) on tumor perfusion and oxygenation. Methods and Materials: Anesthetized Sprague Dawley rats with DS-sarcomas implanted subcutaneously onto the hind foot dorsum were used in this study. Mean arterial blood pressure (MABP) was measured throughout experiments. Regional red blood cell (RBC) flux was monitored using a multichannel laser Doppler device and tumor oxygenation on a more global l…
Pharmacokinetics and absolute bioavailability of oral cefuroxime axetil in the rat.
2000
The objectives of this study were to determine the oral bioavailability of cefuroxime (C) and to evaluate the pharmacokinetic model that best describes the plasma concentration behaviour following single intravenous (IV), intraperitoneal (IP) and oral single doses. The same dose of C was administered by IV, IP and oral routes to three separate groups of rats (2.02 mg of cefuroxime axetil (CA) by the oral route or 1.78 mg of cefuroxime sodium (CNa) by IV and IP route). A two-compartment open model without lag time can predict the C disposition kinetics. The influence of the administration route on the pharmacokinetic parameters and AUC values was investigated by means of a one-way analysis o…
SYNTHESIS, PHYSICO-CHEMICAL AND BIOLOGICAL CHARACTERIZATION OF A PACLITAXEL MACROMOLECULAR PRODRUG
2004
Paclitaxel was attached to poly(hydroxyethylaspartamide) via a succinic spacer arm by a two-step protocol: (1) synthesis of 2'-O-succinyl-paclitaxel; (2) synthesis of PHEA-2'-O-succinyl-paclitaxel. The 2'-O-succinyl-paclitaxel derivative and the macromolecular conjugate were characterized by UV, IR, NMR and mass spectrometry analysis. The reaction yields were over 95% and the purity of products over 98%. Paclitaxel release and degradation from 2'-O-succinyl-paclitaxel occurred at a faster rate at pH 5.5 than 7.4. After 30 h of incubation at pH 5.5 and 7.4 the released free paclitaxel was about 40 and 20%, respectively. In plasma both drug release and degradation were found to occur at a hig…
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…