Nonlinear Pharmacokinetic Modeling to Support Clinical Management of Severe Caffeine Intoxication: A Short Communication

BACKGROUND: Severe caffeine intoxication may result in life-threatening complications and prolonged toxicity due to its saturable metabolism. However, quantitative information regarding the duration of caffeine exposure is limited. Whether nonlinear pharmacokinetic modeling could support the prediction of toxic exposure duration in patients with severe caffeine intoxication was investigated. METHODS: A woman with severe caffeine intoxication was admitted to an intensive care unit. Serial serum caffeine concentrations were measured, and nonlinear pharmacokinetic analysis was conducted using a one-compartment model with Michaelis-Menten elimination. Model-based simulations were conducted to evaluate the concentration-time profiles across a range of initial serum caffeine concentrations. RESULTS: The initial serum caffeine concentration was 140.6 mcg/mL and decreased to 1.7 mcg/mL over 163 hours. Apparent elimination half-life decreased from 42.6 hours during the early phase to 11.2 hours during the late phase, suggesting concentration-dependent elimination. The proportional residual error model provided a better fit than the additive error model. Estimated Vmax and Km were 27.2 mg/h and 17.7 mcg/mL, respectively. The simulations demonstrated a marked concentration-dependent elimination of caffeine. For initial concentrations of 300, 200, and 100 mcg/mL, the predicted times required to decrease below 50 mcg/mL were 248, 154, and 55 hours, respectively. CONCLUSIONS: Nonlinear pharmacokinetic modeling successfully characterized caffeine elimination during severe intoxication and provided quantitative estimates of the duration of toxic exposure. Model-based simulations may support clinical decision making regarding monitoring and treatment strategies by providing quantitative estimates of the duration of toxic caffeine exposure.