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.
Data from sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium are fitted simultaneously using NONMEM and the general linear model, ADVAN 5. Absorption and disposition parameters, serum levels, and absorption profiles were determined. The in vivo absorption profiles were determined using the program TOPFIT. The in vivo absorption for the sustained-release formulation is slow first order and follows a flip-flop model since disposition rate constants are greater than absorption rate constants. Absorption from the enteric-coated form is essentially complete (> or = 95%) at about 7.5 h, while it is 95% complete at 24 h from the sustained-release formulation. This suggests likely absorption from the colon in the case of the sustained-release formulation since absorption is only 75% complete during the first 10 h. The sustained-release relative bioavailability is 90-99%. Absorption from the suppository is essentially complete at about 4.5 h. However, the relative bioavailability of the suppository formulation is low (55%), since defecation may remove the drug from the absorption site before complete absorption.
Idkaidek
N M
NM
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
Amidon
G L
GL
Smith
D E
DE
Najib
N M
NM
Hassan
M M
MM
D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D013488:Suppositories; D013608:Tablets, Enteric-Coated
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D013488:Suppositories; D013608:Tablets, Enteric-Coated; D004008:Diclofenac