Fertility and early embryonic development toxicity and toxicokinetic study of KFP-H008 in Sprague-Dawley rats.

The novel potassium competitive acid blocker, KFP-H008, developed to overcome the shortcomings of proton pump inhibitors. In this study, KFP-H008 was administered by oral gavage at doses of 0 (control), 15, 45, and 150 mg/kg to Sprague-Dawley rats (24 animals per sex per group). Body weight, food consumption, mortality, sexual cycle, mating behavior, pregnancy, sperm motility, and relative organ weights were evaluated. In a concomitant toxicokinetic (TK) study (10 animals per sex per group), plasma TK parameters and tissue distribution of KFP-H008 were tested. There were obvious effects at the dosage of 150 mg/kg to male rats with decreases of prostate weight and lower weight gain; to female rats with lower weight gain, hair off, and lower corpus luteum count. There were no effects on litter parameters. Time to reach maximum plasma concentrations for KFP-H008 was between 0.5 and 1.0 hr for the 15 and 45 mg/kg groups, while for the 150 mg/kg group it had a delay to 2 hr. Overall, the NOAEL of KFP-H008 was considered to be 45 mg/kg in both genders and the TK study shows that exposure (area under the curve) of male rats was about 1,091.0 ± 530.8 μg/Lhr and to female rats was 1,030.5 ± 512.5 μg/Lhr. Administration of KFP-H008although reaches the reproductive organs, it demonstrated no significant effects on reproductive organs, it did not affect mating, fertility, pregnancy, growth, or morphologic development.