Search results for "Kinetic"
showing 10 items of 3064 documents
Rapid in vitro test to predict ocular tissue permeability based on biopartitioning micellar chromatography.
2003
The drug permeability prediction across the ocular tissues is important in the development of new drugs and drug delivery strategies. Physicochemical characteristics of drugs, mainly acid-base character, hydrophobicity and the molecular size determine both their transport across the eye tissue barriers and their retention in biopartitioning micellar chromatography (BMC). An in vitro model able to describe and predict the whole cornea drug permeability is proposed. The model uses the retention of drugs in BMC and molecular weight (MW) as predictive variables. The relationships between drug retention data in BMC and their bibliographic permeability values in stroma, epithelium-plus-stroma and…
Response to Agomelatine Treatment is Independent of Smoking Status and Dosage: Results From the AGOPSYCH Study.
2018
Abstract Introduction Cigarette smoking influences response to antidepressant treatment. It accelerates the metabolism of several cytochrome P450 (CYP) subtypes, including CYP1A2, and therefore bears the risk of pharmacokinetic interactions with psychotropic drugs using that pathway. Agomelatine is a substrate of CYP1A2; the association between nicotine use and agomelatine dosage, however, has never been studied before. Methods Smoking habits were correlated with agomelatine doses and treatment outcomes in a sample of 27 patients with lifetime diagnoses within the schizophrenia spectrum who received agomelatine treatment in addition to their stable antipsychotic treatment regimen because of…
Utilizing inherent fluorescence of therapeutics to analyze real-time uptake and multi-parametric effector kinetics.
2011
Abstract The precise detection of pharmaceutical drug uptake and knowledge of a drug’s efficacy at the single-cell level is crucial for understanding a compound’s performance. Many pharmaceutical drugs, like the model substances Doxorubicin, Mitoxantrone or Irinotecan, have a distinctive natural fluorescence that can be readily exploited for research purposes. Utilizing this respective natural fluorescence, we propose a method analyzing simultaneously in real-time the efficiency, effects and the associated kinetics of compound-uptake and efflux in mammalian cells by flow cytometry. We show that real-time flow cytometric quantification of compound-uptake is reliably measured and that analyzi…
A multilevel object-oriented modelling methodology for physiologically-based pharmacokinetics (PBPK): Evaluation with a semi-mechanistic pharmacokine…
2019
Abstract Background and objective The aims of this study are (i) to assess the predictive reliability of the physiologically based software PhysPK versus the well-known population approach software NONMEM for the cited semi-mechanistic PK model, (ii) to determine whether these modelling approaches are interchangeable and (iii) to compare acausal with causal modelling approaches in the framework of semi-mechanistic PK models. Methods A semi-mechanistic model was proposed, which assumed oral administration of a solid dosage form with a peripheral compartment and two active metabolites. The model incorporates intestinal transit, dissolution limited by solubility, variable efflux transporter ex…
Biopartitioning micellar separation methods: modelling drug absorption
2003
The search for new pharmacologically active compounds in drug discovery programmes often neglects biopharmaceutical properties as drug absorption. As a result, poor biopharmaceutical characteristics constitute a major reason for the low success rate for candidates in clinical development. Since the cost of drug development is many times larger than the cost of drug discovery, predictive methodologies aiding the selection of bioavailable drug candidates are of profound significance. This paper has been focussed on recent developments and applications of chromatographic systems, particularly those systems based on amphiphilic structures, in the frame of alternative approaches for estimating t…
Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”
2021
AbstractMaintaining an adequate level of sedation and analgesia plays a key role in the management of traumatic brain injury (TBI). To date, it is unclear which drug or combination of drugs is most effective in achieving these goals. Ketamine is an agent with attractive pharmacological and pharmacokinetics characteristics. Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the prehospital environment. In this point of view, we discuss different aspects of the use of ketamine in the acute phase of TBI, with its potential benefits and pitfalls.
Isosorbide dinitrate: pharmacokinetics after intravenous administration.
1982
Isosorbide dinitrate (ISDN) is an important organic nitrate found therapeutically useful in its sublingual and oral forms in various cardiovascular diseases such as angina pectoris (1) and congestive heart failure (2). Recently Distante et al. (3) showed that an intravenous infusion of this drug, at 0.021–0.083 mg/min is also effective in managing unstable angina. The availability of an intravenous dosage form of ISDN not only affords the opportunity to characterize the pharmacokinetics of this drug after this particular mode of therapy, but also gives the possibility of assessing the bio-availability of this drug after other (e.g., oral) routes of administration in patients. This latter po…
Interacciones farmacológicas de los fármacos antihipertensivos
2005
A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. Hypertensive patients, mainly the more elderly ones, frequently present concomitant diseases that require the administration of several medicines which facilitates the appearance of interactions. The lack of effectiveness of the antihypertensive treatment is a relatively frequent fact that sometimes is due to interactions of antihypertensive drugs with other treatments. It is difficult to determine the incidence of interactions, but it is related to the number of drugs administered simultaneously. Between 37 and 60% of hospital-admis…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Aciclovir
2008
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. However, in some countries also 800 mg tablets are available which …
Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics
2018
[EN] The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm(2) were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm(2) were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical…