Search results for "therapeutic index"

Biotransformation in vitro of the 22R and 22S epimers of budesonide by human liver, bronchus, colonic mucosa and skin.

2001

The pharmacological effects of glucocorticoids are greatly influenced by their pharmacokinetic properties. In the present report, the in vitro biotransformation of the 22R and 22S epimers of the topical steroid budesonide was studied in the S-9 fraction of human liver, bronchus, skin and colonic mucosa. The disappearance of unchanged epimers of budesonide was measured during 90 min of incubation by high performance liquid chromatography. The rate of disappearance was high in human liver while little biotransformation occurred in bronchial tissue and colonic mucosa, and none was detected in the skin. A marked decay of the initial concentration of unchanged budesonide epimers was noticed afte…

Carbon based nanomaterials for the detection of narrow therapeutic index pharmaceuticals

2020

Precise detection of important pharmaceuticals with narrow therapeutic index (NTI) is very critical as there is a small window between their effective dose and the doses at which the adverse reactions are very likely to appear. Regarding the fact that various pharmacokinetics will be plausible while considering pharmacogenetic factors and also differences between generic and brand name drugs, accurate detection of NTI will be more important. Current routine analytical techniques suffer from many drawbacks while using novel biosensors can bring up many advantages including fast detection, accuracy, low cost with simple and repeatable measurements. Recently the well-known carbon Nano-allotrop…

Nanomedicine: Silver Atomic Quantum Clusters of Three Atoms for Cancer Therapy: Targeting Chromatin Compaction to Increase the Therapeutic Index of C…

2018

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Carbamazepine.

2020

Abstract Literature relevant to assessing whether BCS-based biowaivers can be applied to immediate release (IR) solid oral dosage forms containing carbamazepine as the single active pharmaceutical ingredient are reviewed. Carbamazepine, which is used for the prophylactic therapy of epilepsy, is a non-ionizable drug that cannot be considered “highly soluble” across the range of pH values usually encountered in the upper gastrointestinal tract. Furthermore, evidence in the open literature suggests that carbamazepine is a BCS Class 2 drug. Nevertheless, the oral absolute bioavailability of carbamazepine lies between 70 and 78% and both in vivo and in vitro data support the classification of ca…

Nanocarriers for respiratory diseases treatment: Recent advances and current challenges

2014

Pulmonary delivery of locally-acting drugs encapsulated in nanocarriers provides several advantages for the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis, tuberculosis and lung cancer. These advantages include, among others, sustained drug delivery to the lungs, reduced therapeutic dose and improved patient compliance. The aim of this review is to give an updated overview on recent advances recorded in the last few years in this field as well as on the major challenges still existing and that remain to be overcome before any clinical application. After an outline on the cellular and extracellular barriers affecting drug delivery to…

Influence of Pharmacokinetic Variations on the Pharmacological Properties of Adriamycin

1972

Whenever it appears impossible to modify the chemical structure of drugs with a high and established therapeutic activity but a low chemotherapeutic index, pharmacological research has to find other ways of improving the chemotherapeutic index. This problem is particularly important in the case of antitumor drugs, thus justifying research into the most suitable choice of dosage and routes of administration, as well as into the pharmacological associations which enable tumor cells to be hit at various stages of the reproductive cycle. Alternatively, the therapeutic index could be improved by the use of antagonistic compounds (like, for example, methotrexate and folinic acid) which act upon t…

Inulin-based polymer coated SPIONs as potential drug delivery systems for targeted cancer therapy

2014

This paper deal with the synthesis and characterization of PEGylated squalene-grafted-inulin amphiphile capable of self-assembling and self-organizing into nanocarriers once placed in aqueous media. It was exploited as coating agent for obtaining doxorubicin loaded superparamagnetic iron oxide nanoparticles (SPIONs) endowed with stealth like behavior and excellent physicochemical stability. Inulin was firstly modified in the side chain with primary amine groups, followed in turn by conjugation with squalenoyl derivatives through common amidic coupling agents and PEGylation by imine linkage. Polymer coated SPIONs were so obtained by spontaneous self-assembling of inulin copolymer onto magnet…

QTc Time Correlates with Amitriptyline and Venlafaxine Serum Levels in Elderly Psychiatric Inpatients

2018

Abstract Introduction Many antidepressants cause QT prolongation but the classification of cardiac risk of these drugs varies markedly in different published lists. This retrospective study analyzed the correlation of QTc time with amitriptyline and venlafaxine serum level in elderly psychiatric inpatients. Methods Elderly inpatients aged≥65 years for whom venlafaxine or amitriptyline serum level had been measured were selected retrospectively from a therapeutic drug monitoring database and screened for an electrocardiogram measurement at the time of blood withdrawal. The correlation of amitriptyline or venlafaxine serum levels with QTc time was examined by using Pearson’s correlation analy…

Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions?

2003

Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCA) is established in the treatment of depression to optimize outcome and safety. However, there are few reports on TDM under naturalistic clinical conditions. In the present study, we investigated a TDM group (TDM) and a randomly assigned parallel group without TDM (no-TDM) while on TCA treatment. Serum levels were analyzed in both cohorts, but feedback and dose recommendation were only provided for the TDM group. Serum levels of TCA were assessed by high-performance liquid chromatography (HPLC). The outcome was measured weekly using the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impressions Scale (CGI), and…

Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DAL…

2014

The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The followi…