Omeprazole absorption from a compounded transdermal formulation in healthy volunteers

Objective: To evaluate the plasma concentration versus time profile of omeprazole following the administration of a compounded transdermal gel formulation in healthy volunteers. Design: Single-dose transdermal pharmacokinetic (PK) study including a comparison with historical data from an oral PK study. Setting: Academic clinical research center. Participants: Eight healthy volunteers between 18 and 50 years of age. Interventions: Omeprazole gel 40 mg (0.8 mL) was applied to the ventral surface of the forearm covering an area of 7 x 15 cm without an occlusive dressing. Blood samples were collected just before application and then at 1, 2, 3, 4, 6, and 8 hours. Plasma concentrations of omeprazole were determined using a validated liquid chromatography tandem mass spectrometry method. Main Outcome Measures: PK parameters (maximal plasma concentration [C_max], the time of C _max [T_max], the area under the omeprazole concentration versus time curve from 0 to 8 hours, the elimination rate constant, and the half-life of the elimination phase) following transdermal administration, compared with historical controls who had received an oral omeprazole 40 mg dose during a previous study. Results: Of the eight volunteers, five had undetectable plasma omeprazole concentrations throughout the 8-hour study, precluding a complete PK analysis. For the three volunteers with detectable plasma omeprazole concentrations, the values ranged from 0.204 to 0.552 ng/mL. Including values of 0 for the patients with undetectable levels, the mean (± SD) C_max was 0.153 ± 0.241 ng/mL, and the T _max in patients with detectable levels occurred at approximately 6 hours. The plasma concentrations following transdermal administration were approximately 1,000-fold lower than those observed with oral dosing. Conclusion: Transdermal absorption from a single dose of the omeprazole gel formulation used in this study was poor. This transdermal gel formulation is clearly not bioequivalent to the oral capsule.