デヒドロペプチダーゼ-I (DHP-I) の組織内分布の種差とpanipenemの代謝に及ぼす影響

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  • <I>IN VITRO</I> DEHYDROPEPTIDASE-I ACTIVITY AND ITS HYDROLYTIC ACTIVITY OF PANIPENEM IN SEVERAL TISSUES IN ANIMAL SPECIES AND THEIR INFLUENCE ON THE DISPOSITION OF PANIPENEM <I>IN VIVO</I>

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The influence of dehydropeptidase-I (DHP-I) activity on the elimination of panipenem (PAPM) in vivo was studied by examining glycyldehydrophenylalanine (GDPA) and PAPM hydrolytic activities in several tissues in animal species.<BR>Renal GDPA hydrolytic activity was the highest in mice followed with rabbits, dogs, monkeys and humans, while in rats, it was the highest in the lung.<BR>Tissues with high DHP-I activities have mostly high PAPM hydrolytic activity, which suggests DHP-I is strongly associated with the hydrolytic metabolism of PAPM. On the other hand, since the high DHP-I activity of human kidney has rather low PAPM hydrolytic activity, there exist species differences in substrate specificity of the DHP-I.<BR>In rats, the plasma elimination of PAPM was the fastest accompanying with high plasma concentration of the hydrolytic product among animal species tested.<BR>These results indicate the metabolic disposition of PAPM is deeply dependent on DHP-I activity especially in the lung and the kidney.

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