UNASSIGNED: 1.   In recent years, the minipig is increasingly used as a test species in non-clinical assessment of drug candidates. While there is good scientific evidence available concerning cytochrome P450-mediated metabolism in minipig, the knowledge of other metabolic pathways is more limited. 2.   The aim of this study was to provide an understanding of when, why, and how drug metabolism in minipig differs from other species commonly used in non-clinical studies. In-house cross-species metabolite profile comparisons in hepatocytes and microsomes of 38 Roche development compounds were retrospectively analyzed to compare the metabolism among minipig, @entity1 , @entity35 , @entity235 , monkey, @entity95 and @entity19 . 3.   A significant contributor to the elevated metabolism observed for certain compounds in minipig was identified as @entity6346 hydrolysis. The hepatic @entity6346 hydrolysis activity in minipig was further investigated in subcellular liver fractions and a structure-activity relationship was established. When structural motifs according to the established SAR are excluded, coverage of major @entity1 metabolic pathways was shown to be higher in minipig than in @entity235 , and only slightly lower than in @entity5434 . 4.   A strategy is presented for early identification of drug compounds which might not be suited to further investigation in minipig due to excessive hydrolytic metabolism.

Shedding light on minipig drug metabolism - elevated XXXX hydrolysis in vitro.

@entity1 :: ('9606', 'Species') :: ['human'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity235 :: ('9615', 'Species') :: ['dog'] @entity5434 :: ('9541', 'Species') :: ['cynomolgus monkey'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity6346 :: ('CHEBI:32988', 'Chemical') :: ['amide']
@entity6346 :: (CHEBI:32988,Chemical) :: ['amide']
