Determination of the population pharmacokinetic parameters of sustained‐release and enteric‐coated oral formulations, and the suppository formulation of diclofenac sodium by simultaneous data fitting using NONMEM

Diclofenac pharmacokinetic meta‐analysis and dose recommendations for surgical pain in children aged 1–12 years

“…Diclofenac absorption from immediate‐release formulations can be highly variable, with double and sometimes multiple peaks being observed in some subjects (28). This erratic absorption, probably caused by variability in pH‐dependent dissolution, was described using an empirical dual‐absorption model, which has previously been shown to fit diclofenac immediate‐release data (14,18). Fixing the disposition parameters ensured that any misspecification in the absorption model did not affect the volume and CL parameters.…”

“…Absorption model building first involved visual inspection of the concentration–time curves for each extravascular formulation. Where multiple peaks were observed, a dual‐absorption compartment model was used (14). The dual‐absorption model entails giving a full dose to each compartment; the following relationships ensuring only a maximum of one full dose could enter the central compartment: where F 1 and F 2 are the bioavailabilities from the first and second depot, respectively, F 1FR is an estimated parameter constrained between 0 and 1 relating to the fraction of dose coming from the first depot compartment, and F is an estimated parameter relating to the overall bioavailability.…”

Gordon L. Amidon: Very Sustained Drug Absorption

“…By the late 1970s, Gordon was motivated to look at oral absorption much more mechanistically and turned his career interest in the direction of mechanistic mass transport analysis . This became a common theme for much of his later research work . Through the 1980s, he studied nutrient digestion and absorption, particularly for amino acids and peptides .…”

Evolution of a Detailed Physiological Model to Simulate the Gastrointestinal Transit and Absorption Process in Humans, Part II: Extension to Describe Performance of Solid Dosage Forms

“…The highly variable lag time between diclofenac ingestion and its appearance in plasma observed in vivo was assumed to be due to differences in the GET of the solid dosage form. 35,45 The effect of variable residence times on individual plasma concentration-time profiles of enteric-coated diclofenac was investigated in a sensitivity analysis. Using the same model, individual plasma concentration-time profiles of diclofenac administered as enteric-coated tablets were predicted for GETs varying between 0 and 200 min.…”