ABSTRACT
The development of genomics in the last decade opened new perspectives to fulfill the permanent ideal of therapy, namely personalization of therapy (of medicine) by using of adage: "the right drug to the right patient". The pharmacogenomics, developed in these 10 years, already permitted the identification of the patients with side drug effects risk by detection of the presence of single nucleotide polymorphisms (SNPs) from enzymatic systems implied in drugs metabolism such as CYP450. More recently, the emergence of pharmacometabonomics permitted the appreciation of the influence of the metabolic factors (and of the environment) on the genes expression. The combination of these sciences can permit a better individualization of drug therapy concerning both the genetic background of individual and exterior interventions. Actual studies seem to confirm this supposition.
Subject(s)
Biotransformation/physiology , Pharmacogenetics/methods , Biotransformation/genetics , Clinical Trials as Topic , Environment , Forecasting , Humans , Precision Medicine/trendsABSTRACT
This paper presents results of a pharmacokinetics study concerning pentoxifylline and its main metabolites after administration of extended release formulation of Trental 400 mg and correlation of this pharmacokinetics with in vitro dissolution test results of parent drug. In order to establish most relevant in vitro test, dissolution was performed in different experimental conditions (stirring rate and dissolution medium). Correlation was linear and very good. Generalization of correlation to rate of appearance of metabolites in plasma proved that this process could be well correlated with dissolution. Most relevant test was finally found to be the release in water medium, in conditions of a high stirring rate - 100 rpm.
ABSTRACT
Our studies focused on the cytomorphological and ultrastructural analysis of ten synovial fluid (S.F.) samples from patients with serum positive rheumatoid arthritis (R.A.) (latex 1/1280, 1/640 and Waaler-Rose 1/1024, 1/1512) as compared to five S.F. sampes from patients with peripheral ankylotic spondylarthritis (A.S.). The cytomorphological investigation aimed at defining the cellularity, ragocytosis and synoviocytogram. We found out that the average number of cells (R.A. = 8060/mm3; A.S. = 6100/mm3), percentage of ragocytes (R.A. = 75%; A.S. = 25%), polymorphonuclear cells (R.A. = 70%; A.S. = 58%), degradative polymorphonuclear cells (R.A. = 7%, A.S. = 3%) and phagocytic mononuclear cells (R.A. = 16%; A.S. = 13%) are by far larger in R.A. than in A.S., whereas the lymphocyte percentage is much more reduced (R.A. = 13%; A.S. = 26%). Ultrastructurally, the rheumatoid S.F. ragocytes present specific intracytoplasmic inclusions and phagolysosomes pointing to an endocytotic activity. At the level of the degradative polymorphonuclear cells (7% cytomorphologically confirmed), the alteration of the granular-fibrillar structure of the nucleus and the presence of some cytoplasmic lysis areas were associated with the absence of cellular organelles. We also noticed cellular and collagen detritus. In A.S. the ultrastructural effect on the polymorphonuclear cells is much more reduced (3%) as compared to R.A. and resides in the dilatation of both mitochondrial cristae and granularendoreticular cisternae as well as in a slight concentration of the fibrogranular nuclear matter. The cells are considerably active in endocytosis. The phagocytotic mononuclear cells of the rheumatoid S.F. and A.S. are morphologically identical to the immunologically activated macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
