Thacker, David L.Modak, AnilNguyen, Phuong D.Flockhart, David A.Desta, Zeruesenay2015-11-132015-11-132011-11Thacker, D. L., Modak, A., Nguyen, P. D., Flockhart, D. A., & Desta, Z. (2011). Stereoselective Pharmacokinetics of Stable Isotope (+/−)-[13C]-Pantoprazole: Implications for a Rapid Screening Phenotype Test of CYP2C19 Activity. Chirality, 23(10), 904–909. http://doi.org/10.1002/chir.21011https://hdl.handle.net/1805/7445AIMS: We have previously shown that the (±)-[(13) C]-pantoprazole breath test is a promising noninvasive probe of CYP2C19 activity. As part of that trial, plasma, breath test indices and CYP2C19 (*2, *3, and *17) genotype were collected. Here, we examined whether [(13) C]-pantoprazole exhibits enantioselective pharmacokinetics and whether this enantioselectivity is correlated with indices of breath test. METHODS: Plasma (-)- and (+)-[(13) C]-pantoprazole that were measured using a chiral HPLC were compared between CYP2C19 genotypes and correlated with breath test indices. RESULTS: The AUC( 0-∞) of (+)-[(13) C]-pantoprazole in PM (*2/*2, n = 4) was 10.1- and 5.6-fold higher that EM (*1/*1or *17, n = 10) and IM (*1/*2or *3, n = 10) of CYP2C19, respectively (P < 0.001). The AUC( 0-∞) of (-)-[(13) C]-pantoprazole only significantly differed between PMs and EMs (1.98-fold; P = 0.05). The AUC( 0-∞) ratio of (+)-/(-)-[(13) C]-pantoprazole was 3.45, 0.77, and 0.67 in PM, IM, and EM genotypes, respectively. Breath test index, delta over baseline show significant correlation with AUC( 0-∞) of (+)-[(13) C]-pantoprazole (Pearson's r = 0.62; P < 0.001). CONCLUSIONS: [(13) C]-pantoprazole exhibits enantioselective elimination. (+)-[(13) C]-pantoprazole is more dependent on CYP2C19 metabolic status and may serve as a more attractive probe of CYP2C19 activity than (-)-[(13) C]-pantoprazole or the racemic mixture.en-USIUPUI Open Access PolicyBreath testGenotypePharmacokineticsRacemicArticle