Pharmacokinetic modeling study demonstrates exact and simplified infusion schedules in animal models, indicating reliable control over targeted drug concentrations in blood.
Key Points
Derive a general analytical method using impulse analysis to calculate intravenous infusion schedules that produce predefined blood concentration profiles over time.
Applied Laplace transform techniques to input-output impulse responses to formulate exact input schedules for constant, linear, and exponential target profiles.
Developed simplified approximate infusion formulations that achieve target concentrations following an initial transient phase.
Validated the derived schedules using experimental pharmacokinetic data for [14C]EDTA-Ca in anesthetized rhesus monkeys and 2-deoxy-D-[1-14C]glucose in conscious rats, accompanied by error analyses.
Derived exact mathematical equations specifying the infusion rates needed to produce constant, linearly increasing, exponentially decaying, and exponentially increasing blood concentration time courses.
Demonstrated that simplified approximate schedules effectively reach and maintain the target blood concentration profile shortly after delivery begins across both animal models.