ABSTRACT
Eighteen normal cats were randomly allocated into two blocks with three treatment groups and dosed orally with clindamycin aqueous solution for 10 days at a dosage rate of 5.5 mg/kg twice daily (Group 1), 11 mg/kg twice daily (Group 2), or 22 mg/kg once daily (Group 3). At the end of dosing, all cats were killed and tissues were taken for clindamycin concentration analysis. Clindamycin was extracted from tissues using solid-phase extraction columns followed by microbiological assay of clindamycin using a cylinder plate assay using M. luteus. Recovery from each tissue was determined by inoculating known concentrations of clindamycin into drug-naive tissues and comparing the observed concentration from the expected concentration. Confirmation that the bioassay detected clindamycin and not N-desmethylclindamycin, its active metabolite, was done using gas-chromatography-mass-spectrometry. Concentrations were highest in the lung, with tissue:serum ratios greater than 3 in all groups. Concentrations were higher in Group 3 than Group 1 (P less than 0.05). Only liver concentrations in Group 3 were statistically higher than in Group 2, although all tissues except bone marrow and CSF had numerically higher concentrations in Group 3 than Group 2. The tissue:serum ratio was greater than 1 in all tissues studied except bone, cerebrospinal fluid, brain, and skeletal muscle.
Subject(s)
Cats/metabolism , Clindamycin/pharmacokinetics , Administration, Oral , Animals , Clindamycin/administration & dosage , Female , Male , Random Allocation , Tissue DistributionABSTRACT
Four multiparous Holstein cows were utilized to determine the effects of high doses of recombinant bovine somatotropin (rbSt) on milk production, feed intake, somatotropin concentration in milk, blood and urine constituents and the presence or absence of treatment-related lesions. Treatments were 0 (control) or 430 mg rbSt daily for 21 days as im injections beginning approximately 150 days into lactation. Cows were fed concentrate according to level of milk production and corn silage ad libitum. Milk yield of rbSt-treated cows increased 34% while dry matter intake and net energy intake decreased. Serum and milk bSt concentrations were elevated following treatment. Red blood cell count, hemoglobin, and hematocrit decreased in rbSt-treated cows; however, values remained within the normal range. Blood urea nitrogen concentration was decreased following treatment. Serum alkaline phosphatase activity, insulin and glucose concentrations were increased in 1 treated cow. No changes were observed in serum thyroxine, cortisol or bSt antibody concentrations. Evidence of irritation at the injection site was examined microscopically and was consistent with irritant swelling. Fetuses of rbSt-treated cows were normal, and cows did not abort. No serious adverse effects were observed following daily injections of 430 mg rbSt.
Subject(s)
Growth Hormone/adverse effects , Lactation/drug effects , Animals , Antibodies/immunology , Blood Cell Count , Body Weight , Cattle , Female , Growth Hormone/administration & dosage , Growth Hormone/blood , Milk/metabolism , Pregnancy , Recombinant Proteins/adverse effects , ReproductionABSTRACT
Bovine somatotropin (bSt) was given either orally or subcutaneously to groups of female hypophysectomized rats daily for 9 days. Ten rats per dose group were given oral dosages of 0 (buffered-water vehicle control), 40, 400, 2000, and 4000 micrograms of bSt per day. Similar groups of ten rats each received subcutaneous doses of 0 (buffered-water vehicle control), 15, 30, and 60 micrograms of bSt per day. Rats were weighed daily to observe their body-weight gain, which is a measure of the biological activity of bSt in the hypophysectomized rat. At study termination, serum of treated rats was monitored for the presence of bSt and antibody to bSt. Bovine somatotropin was detected in the serum of the subcutaneously treated rats, but not in those rats treated orally. Of 18 rats treated subcutaneously with bSt, 14 developed antibodies to bSt, whereas of 38 rats treated orally with bSt, 11 developed antibodies. Subcutaneously treated rats grew in a dose-related manner as expected in this assay. Orally administered bSt failed to elicit a growth response at any dose in this sensitive bioassay system. The data suggest that neither bSt nor growth-promoting fragments of bSt are absorbed after oral administration of doses up to 40,000 micrograms/kg/day in the hypophysectomized rat.
