Search results for "Availability"
showing 10 items of 510 documents
Nonlinearities in amoxycillin pharmacokinetics. II. Absorption studies in the rat.
1992
Most factors influencing amoxycillin oral absorption are, even today, unknown. Since many dosage schedules have been shown to lead to incomplete absorption, it would be desirable to find a suitable animal model where these factors could be studied in depth. In this paper, it is shown that, in the rat, plasma level curves obtained after oral doses of 7 and 28 mg kg-1 are poorly fitted using first-order absorption kinetics and that the best fit is obtained through the use of an input equation combining zero and first-order kinetics. In contrast, plasma level curves found after intraduodenal administration of amoxycillin solutions (7 mg kg-1) are well fitted by first-order input kinetics. It w…
Improvement of trospium-specific absorption models for fasted and fed states in humans
2014
The purpose of this study was to mechanistically interpret the oral absorption pattern of trospium in fasted and fed states by means of gastrointestinal simulation technology. A drug absorption model was built on the basis of experimental data. According to the generated model, low permeability across the intestinal epithelium, delayed gastric emptying time and a prolonged residence time in the small intestine are the key factors governing trospium absorption in the fasted state. Furthermore, in silico modelling provided a plausible explanation of the pronounced reduction in the oral bioavailability of trospium when administered with food. The simulation results support the decreased dissol…
Mechanistic investigation of food effect on disintegration and dissolution of BCS class III compound solid formulations: the importance of viscosity
2012
A negative food effect, i.e. a decrease in bioavailability upon the co-administration of compounds together with food, has been attributed particularly with high solubility/low permeability compounds (BCS class III). Different mechanisms have been proposed including intestinal dilution leading to a lower concentration gradient across the intestinal wall as well as binding of the active pharmaceutical ingredient to food components in the intestine and thereby decreasing the fraction of the dose available for absorption. These mechanisms refer primarily to the compound and not to the dosage form. An increase in viscosity of the dissolution fluid will in particular affect the absorption of BCS…
Long-term expression of the human alpha1-antitrypsin gene in mice employing anionic and cationic liposome vector.
1997
The complete process of gene therapy involves three important steps: targeting, delivery, and gene expression. Since each step can be related to the pharmacological concept of affinity, bioavailability, and intrinsic capacity, this commentary examines, from this perspective, the efficiency of anionic and cationic liposomes as vectors for the in vivo gene transfer of the human alpha1-antitrypsin gene. Small liposomes represent the first generation of liposomes destined for the liver parenchymal cell. Although the final efficiency of gene transfer is low, we found that small liposomes are a kind of high-affinity hepatocyte-destined vector because the dose range for mediating the response is t…
Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity
2003
Aims The aim of this study was to assess the influence of concomitant caffeine intake on the pharmacokinetics of oral melatonin, a probe drug for CYP1A2 activity. Methods Twelve healthy subjects, six smokers and six nonsmokers, were given melatonin (6 mg) either alone or in combination with caffeine (3 × 200 mg). Blood samples for the analysis of melatonin or caffeine and paraxanthine were taken from 1 h before until 6 h after intake of melatonin. Subjects were genotyped with respect to the CYP1A2*1F (C734A) polymorphism. Results When caffeine was coadministered the Cmax and AUC of melatonin were increased on average by 142% (P = 0.001, confidence interval on the difference 44, 80%) and …
In vitro–in vivocorrelations: general concepts, methodologies and regulatory applications
2015
The major objective of in vitro-in vivo correlations is to be able to use in vitro data to predict in vivo performance serving as a surrogate for an in vivo bioavailability test and to support biowaivers. Therefore, the aims of this review are: (i) to clarify the factors involved during bio-predictive dissolution method development; and (ii) the elements that may affect the mathematical analysis in order to exploit all information available. This article covers the basic aspects of dissolution media and apparatus used in the development of in vivo predictive dissolution methods, including the latest proposals in this field as well as the summary of the mathematical methods for establishing …
Influence of emulsified fat on chlorpromazine availability in rabbit blood.
1974
Kaninchen uberlebten die letale Dosis von 30 mg/kg Chlorpromazin (i.v.) nur zusammen mit einer Fettinfusion (0,5 ml/kg/min Lipofundin S 10®). Es konnte in vitro gezeigt werden, dass der Zusatz einer Fettemulsion (Lipofundin S 10®) zu Kaninchenblut (25 mg Fett/ml) den Anteil an freiem Chlorpromazin (Gesamtkonzentration 10−4M) von 2,05% auf 0,87% herabsetzt.
In silicoprediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen
2012
The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient …
Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.
1997
Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solutio…
Evidence of a flip-flop phenomenon in acamprosate pharmacokinetics: an in vivo study in rats.
2006
The pharmacokinetics of acamprosate were examined in the rat after oral and intravenous administration in order to detect the possible presence of a flip-flop phenomenon. Rats received 9.3 or 73.3 mg/kg of the drug as an intravenous bolus. The same doses were orally administered via gastric intubation. Plasma samples were taken from the jugular vein for determination of acamprosate concentration by liquid scintillation counting. The drug content was also quantified in urine and faeces. The acamprosate bioavailability was close to 20%, the amount recovered in the faeces being around 80% of the administered dose. The terminal slope of the oral plasma curve was significantly lower than that ob…