The dynamics of nonsteroidal anti-inflammatory therapy for primary dysmenorrhea

The dynamics of drug therapy are generally discussed in terms of absorption, excretion, and blood levels. These established methods of analyzing the pharmacodynamics frequently fail to determine the more critical tissue concentrations necessary for ultimate drug action. The use of intrauterine pressures to objectively measure uterine response to drug therapy may be used to demonstrate the onset and magnitude of drug action in nonsteroidal anti-inflammatory drug therapy for patients with primary dysmenorrhea. When continuous intrauterine pressure data is combined with plasma drug level sampling, a reflection of the dynamics of these drugs may be possible. Data were studied from 18 patients who participated in a double-blind, placebo-controlled, single-dose crossover study of subjective and objective responses to meclofenamate. The responses in these patients indicated a clear parallel in time response curves between plasma drug level and alterations in uterine contractile activity. The slight time delay between the changes in blood drug level and the onset of changes in uterine activity is hypothesized to represent the time necessary to establish effective tissue levels. Examples of time response curves are illustrated.