Pharmacokinetics and pharmacodynamics in the design of controlled-release beads with acetaminophen as model drug.

Relationships between pharmacodynamics (drug concentration and effect) and pharmacokinetics were used to develop an oral, controlled-release-bead dosage form. Reported pharmacodynamic data were used with pharmacokinetic curves to identify effective therapeutic drug concentrations for optimum therapy for a drug with a "deep tissue" effective compartment. The commonly used, over-the-counter, non-narcotic, analgesic-antipyretic acetaminophen (APAP) was used as the model drug. Data reported in the literature were used to compare analgesic and antipyretic efficacy. Computer simulations were performed with MAXSIM (version 3.01) to suggest a zero-order drug release useful for a 12-h, oral, sustained-dosage form for antipyretic therapy in children, on the basis of current pediatric dosing of APAP. Coated APAP beads with the desired release rate were then developed with fluid-bed coating technology.