Burroughs Welicome Scholar in Clinical Pharmacology. References

curve for calculation of results. Therefore, reliable results can be obtained with a simple recorder, and more expensive integrators are not required. Paraxanthine, a metabolite of caffeine, is co-eluted with theophylline. Therefore, precise measurement of theophylline in plasma cannot be obtained in subjects exposed to caffeine. This is a known limitation of most reversed-phase chromatographic methods for methyl-xanthines. Alternative methods have been used to solve this problem. Adequate resolution can be obtained with normal-phase chromatography or, preferably, by adding an ion-pair reagent to reversed-phase chromatography (5, 8, 9). We have not addressed this issue because it was not pertinent to our specific application. We have applied this method successfully to measure methylxanthines in only 10 L of plasma. This may have particular application in neonates and small animals. More-over, we can reliably measure concentrations of caffeine in tissue after its oral administration. The rat is a widely used model to study the behavioral effects of caffeine, as well as its potential toxicology. In addition, methylxanthines have been used as potential pharmacological probes to study the role of adenosine in physiological and pathological processes (10, 11). For each of these applications it is important to determine the concentrations of caffeine achieved at rele-vant tissue sites, because concentrations in tissue may correlate better with caffeine actions than do caffeine intake or concentrations in plasma. The tissue concentrations of caffeine obtained in this study (slightly <100 ano1fL) approximate the Kd found in in-vitro studies for adenosine receptor antagonism (12). We thank Mrs. Dorothea Boemer and Mr. Bolton Smith for their help in preparing the manuscript and Mr. Bahrat Patel and Mrs. Suzanna Lonce for excellent technical assistance. Tha work was supported by grants HL-34021, HL37961, and RR00095 from the National Institutes of Health. I. B. was a clinical associate physi