NEW METHODS FOR COMPARISON OF ERYTHROCYTE SEDIMENTATION CURVES IN ESTIMATION OF AGGREGANT AND ANTIAGGREGANT EFFECTS OF DRUGS.

Tests of erythrocyte sedimentation provide a measure of the acute phase response to inflammatory diseases, most infections, in cancer, cardiovascular and many other diseases. The term erythrocyte sedimentation rate (ESR) is retained because of traditional usage, although a single measurement after 60 minutes is not a rate Recommendations of International Council for Standardization in Haematology (ICSH) considers ESR as defined by the height of sedimented column of erythrocytes at a given time (usually one hour). Single parameter characterization of sedimentation of erythrocytes by ESR represents a course approach of complex phenomena. The simplicity of the sedimentation rate is only apparent. In practice, a lot of difficulties arises in definition of the "rate" since its estimation requires at least two points on the sedimentation curve. If the sedimentation does not start immediately, a positive lag-time appearing, ESR measured value at one hour is a rate lower than the real slope, estimated from sedimentation curve. If sedimentation is more rapid and curve reach saturation before one hour, the real rate, defined by sedimentation curve is greater than the rate defined by official ESR. A more in depth analysis of data started in the paper from "sedimentation curves" which characterise dynamic evolution in time of phenomena. Comparison of curves arises great difficulties even for mathematicians. Metrics in the spaces of curves implies a more advanced mathematics. Consequently, sedimentation curves where replaced by some of their global parameters such as initial slope or area under curve. Further for comparison of curves were introduced some specific methods from cancer research, biopharmacy and pharmacokinetics. It concerns the rate of sedimentation this was estimated from the initial slope of the curves. In fact the curve could be modelled for a longer time interval using a twophase linear regression. The slope of the first line could define better the ESR. If we consider evolution of height of sediment as a "survival curve", the Kaplan Meyer method becomes immediately applicable. From dissolution studies in biopharmacy the official metric on the release curves space, based on the sum of squared differences between matched points of the sedimentation curves. A set of methods (linear regression in estimation of the slopes, of the similarity of curves using f2 metrics, of time-lag, of half-time etc.), as well as comparison of Areas Under Sedimentation Curves, were applied in evaluation of clopidogrel's effect at concentrations between 1 and 8 μg/ml. [ABSTRACT FROM AUTHOR]