Effects of in vivo treatment with a new fluorinated macrolide (P-0501A) and other erythromycins on drug clearance and hepatic functions in perfused rat liver.
1986
: The hepatic clearance and the effects of a new fluorinated macrolide (P-0501A) on the functions of the isolated, perfused rat liver were compared with two known erythromycins--the base and the estolate--after 7 days of treatment (1.36 mmol/kg po daily). The in vitro metabolism of the antibiotics was induced to different extent but only the base and P-0501A were cleared from the perfusate and the liver faster than in untreated animals. In untreated rats the therapeutically active form of P-0501A was excreted in the bile more than the base and the estolate; after pretreatment, biliary excretion of all erythromycins was nearly double. The content of inactive, complexed cytochrome P-450 was increased only by the base and estolate, with various effects on microsomal activities (some induced, e.g. aminopyrine demethylation, other reduced, e.g. pentobarbital clearance). The clearance and biliary excretion of sulphobromophthalein was not affected by treatment with P-0501A or the base, but was significantly reduced by estolate.
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