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
✍ Scribed by Nasir M. Idkaidek; Gordon L. Amidon; David E. Smith; Naji M. Najib; Mazen M. Hassan
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 140 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
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 ( ]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 sustainedrelease 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.