Rapid determination method of caffeine and application to monitoring of caffeine-assisted chemotherapy

Caffeine-assisted chemotherapy for bone and soft tissue tumours is very effective. However, high serum caffeine concentrations cause severe side effects, so monitoring of the serum level during therapy is important. For this purpose, a rapid determination method was established by high-performance liquid chromatography after solid-phase extraction. This method can measure caffeine and its three major metabolites in serum samples within 8 min. The mean serum caffeine concentrations of patients were 34.6 +/- 7.8, 54.5 +/- 11.9 and 73.0 +/- 12.8 mug/ml at 24, 48 and 72 h, respectively, after the start of a 1500 mg/m(2)/day continuous infusion for 72h. The distribution volume of caffeine was 0.65 +/- 0.23 l/kg, and the total body clearance was 0.025 +/- 0.011 l/h/kg, which was one-third of the reported low dose clearance. The appropriate infusion rate was calculated to avoid severe side effects in the final phase of the infusion by using a one-compartment constant infusion model based on the serum levels measured at 24 and 48 h. Caffeine clearance did not correlate with the metabolite/caffeine ratio in serum at any time. It is concluded that individual monitoring with this method for the purpose of dose adjustment is useful for avoiding the side effects of caffeine-assisted chemotherapy. Copyright (C) 2004 John Wiley Sons, Ltd.