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  • Title: Differential stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor in extensive and poor metabolizers of pantoprazole--a preliminary study.
    Author: Tanaka M, Yamazaki H, Hakusui H, Nakamichi N, Sekino H.
    Journal: Chirality; 1997; 9(1):17-21. PubMed ID: 9094198.
    Abstract:
    Pantoprazole (PAN) is a proton pump inhibitor that is administered as a racemic mixture. The pharmacokinetics of PAN enantiomers were investigated in extensive metabolizers (EMs) and apparent poor metabolizers (PMs) of PAN who received a single, 40, 60, or 80 mg oral dose of racemic PAN as enteric-coated formulation. In the EMs, the serum concentrations of (-)-PAN were slightly higher than those of (+)-PAN at each dose level. The (+)/(-) ratios for the area under the concentration-time curve (AUC) and the half-life were 0.58-0.89 and 0.62-0.88, respectively. In the PMs, the serum concentrations and both enantiomers were much higher than those in the EMs at each dose level and significant differences in pharmacokinetics of (+)- and (-)-PAN were observed. The half-lives for (+)-PAN were 2.67-3.77 times longer than those for (-)-PAN. The AUCs for (+)-PAN were 2.65-3.45 times greater than those for (-)-PAN. Therefore, the metabolism of (+)-PAN is impaired to a greater extent than (-)-PAN in the PMs, which resulted in the stereoselective disposition of PAN in the PMs. It has been suggested that the EMs and the PMs of PAN could be differentiated by determining the (+)/(-) enantiomer ratio in serum at one time point, possibly 2-6 h after oral dosing, because the (+)/(-) enantiomer ratios in the PMs were opposite those in the EM subjects.
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