1. PHARMACOKINETIC STUDY OF OMEPRAZOLE MULTI-UNIT PELLET SYSTEM (LOSEC MUPS®) VERSUS EXTEMPORANEOUS BICARBONATE FORMULATION IN PATIENTS WITH CEREBRAL PALSY M. Van Winckel *, J. De Smet °, K. Boussery °, P. De Cock **, N. Huyghebaert °, P. De Paepe °°, J.-P. Remon °, and J. Van Bocxlaer ° Ghent University Hospital, Paediatric Gastroenterology Dpt.*, Hospital Pharmacy Dpt** Ghent University, Faculty of Pharmaceutical Sciences°, Heymans Institute of Pharmacology°°
1. Introduction
In patients with tube feeding, the proton pump inhibitor omeprazole is often used off-label as an extemporaneous formulation (8.4 % bicarbonate suspension). Few pharmacokinetic data on the use of this suspension are available.
2. Aim
The aim of this study was to compare the pharmacokinetics of omeprazole extemporaneous formulation with omeprazole MUPS®.
3. Methods
Study population
10 patients with cerebral palsy and mental retardation, treated with omeprazole because of esophagitis grade B-D
7 female, age 7 – 26 years
Study design
randomized cross-over design
standard omeprazole dose (20 or 40 mg) was administered for a 14 day-period as Losec MUPS® (tablet disintegrated in 10 ml water), followed by a 14 day-period as a 8.4% bicarbonate suspension, or vice versa
both formulations were administered through the gastrostomy tube, in accordance to local guidelines
on day 15 and day 29, venous blood samples were drawn predose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 hours postdose
omeprazole plasma levels were determined by hydrophilic interaction chromatography with tandem mass spectrometry (HILIC-MS/MS)
Fig. 1: plasmaconcentration-time profile for omeprazole administered as MUPS® and as bicarbonate suspension in patient 2
Fig. 2: plasmaconcentration-time profile for omeprazole administered as MUPS® and as bicarbonate suspension in patient 8
in all patients, tmax was shorter with suspension vs MUPS® (table 1)
4. Results
5. Conclusion
in 7/10 patients, AUC and Cmax were at least doubled after administration of suspension compared to MUPS® (table 1 , patients marked in yellow)
in 3/10 patients, administration of MUPS® resulted in higher AUC and Cmax compared to suspension (table 1 , patients marked in blue)
Even though interindividual variability in omeprazole-pharmacokinetics is substantial, the 8.4 % bicarbonate suspension shows a consistently shorter tmax compared to MUPS®, with bio-availability being better for suspension in 7/10 patients with cerebral palsy and mental retardation.
Table 1: patient characteristics and pharmacokinetic parameters for omeprazole after administration as bicarbonate suspension and as Losec MUPS®