A study was made to determine the effect of Haemonchus contortus
parasitic infection in lambs on the clearance of several IV administered drugs. Clearance of
sulfobromophthalein or
sulfathiazole from the plasma of lambs was unaffected by
infection with H contortus. Clearance of
antipyrine was enhanced by the
infection, and
thiabendazole treatment did not alter this effect. Clearance of
chloramphenicol (CAP), administered as the
succinate ester (CAPS), was not changed by the
infection, but it was increased
after treatment with
thiabendazole. Changes in the mean body residence time and initial plasma concentration of CAPS and CAP
after treatment with
thiabendazole indicate that hydrolysis of CAPS to CAP was reduced. High concentrations of CAPS apparently enhanced its own elimination directly rather than via the expected sequence involving hydrolysis, glucuronidation, and excretion of CAP-
glucuronide. Enhanced clearance of
antipyrine following
infection of lambs with H contortus can be explained in at least 2 ways. First, it is possible that the lambs did not have mature amounts of hepatic
drug metabolizing
enzyme activity as reported by other investigators, which may be explained by breed differences or animal husbandry practices. Second,
infection of lambs by H contortus may have triggered an inductive response in hepatic
cytochrome P-450-mediated activities, which might result via a generalized enhancement in hepatic
protein synthesis associated with the physiologic response to replace
plasma proteins and other blood components lost through
gastrointestinal hemorrhage caused by the active feeding of adult worms. Other phase-II reactions such as acetylation, glucuronidation, and
glutathione-S-transferase apparently were not affected.