Effect of chronic lead intoxication on the distribution and elimination of amoxicillin in goats

A study of amoxicillin pharmacokinetics was conducted in healthy goats and goats with chronic lead intoxication. The intoxicated goats had increased serum concentrations of liver enzymes (alanine aminotransferase and gamma-glutamyl transferase), blood urea nitrogen, and reactivated delta-aminolevulinic acid dehydratase compared to the controls. Following intravenous amoxicillin (10 mg/kg bw) in control and lead-intoxicated goats, elimination half-lives were 4.14 and 1.26 h, respectively. The volumes of distribution based on the terminal phase were 1.19 and 0.38 L/kg, respectively, and those at steady-state were 0.54 and 0.18 L/kg, respectively. After intramuscular (IM) amoxicillin (10 mg/kg bw) in lead-intoxicated goats and control animals, the absorption, distribution, and elimination of the drug were more rapid in lead-intoxicated goats than the controls. Peak serum concentrations of 21.89 and 12.19 microg/mL were achieved at 1 h and 2 h, respectively, in lead-intoxicated and control goats. Amoxicillin bioavailability in the lead-intoxicated goats decreased 20% compared to the controls. After amoxicillin, more of the drug was excreted in the urine from lead-intoxicated goats than the controls. Our results suggested that lead intoxication in goats increases the rate of amoxicillin absorption after IM administration and distribution and elimination. Thus, lead intoxication may impair the therapeutic effectiveness of amoxicillin.

Modification of pharmacokinetics of cefotaxime in uranyl nitrate-induced renal damage in black bengal goats

Pharmacokinetics of cefotaxime (50mg/kg, i.m.) were studied in both healthy and kidney damaged female black Bengal goats. Uranyl nitrate (0.75mg/kg) was administered intravenously, once daily for five consecutive days to induce kidney damage. The pharmacokinetic variables were calculated in both cases. Kidney damage caused several changes in the determined variables. The Cmax and Cmin of cefotaxime observed at 0.50 and 5 h in normal goats were 24.91+/-1.51 and 1.22+/-0.07 microgram/ml, respectively, while the same in kidney damaged goats at 1 and 72 h were 75.00+/-0.45 and 3.10+/-0.09 microgram/ml, respectively. Renal damage condition significantly increased t1/2,ka (0.48+/-0.01 h), t1/2,ke (20.03+/-0.16 h), AUC (2440.10+/-24.26 microgram. h/ml) and significantly decreased Vdarea (0.59+/-0.007L/kg), Vss (0.58+/-0.007 L/kg) and ClB (0.02+/-0.008 L/kg/h) values of cefotaxime compared to normal goats.

An ultrastructural study on cytotoxic effects of mono(2-ethylhexyl) phthalate (MEHP) on testes in Shiba goat in vitro

In this study, the effects of mono(2-ethylhexyl) phthalate (MEHP), one of metabolites of di(2-ethylhexyl) phthalate, on immature Shiba goat testes in vitro were examined. The testes of 2-month-old Shiba goats were cut into smaller pieces, and seeded in medium. At 1, 3, 6 and 9 hr after administration of MEHP at various concentrations (0, 100 nmol ml-1, 1 nmol ml-1, and 1 x 10-3 nmol ml-1, respectively), the specimens were obtained for light and transmission electron microscopic observations. As a result, at 1 hr after exposure to MEHP, the vacuolization and nuclear membrane rupture appeared in Sertoli cells. Such alterations tended to gradually increase in number in timeand dose-dependent manners. Moreover, by MEHP treatment, apoptotic spermatogenic cells (characterized with chromatin condensation, cytoplasm shrinkage without membrane rupture, still functioning cell organelles, and packed cell contents in membrane-bounded bodies), apoptotic Sertoli cells (characterized with nuclear membrane lysis, nuclear condensation), necrotic spermatogenic cells (characterized with swollen and ruptured mitochondria, plasma membrane lysis, spilt cell contents, and chromatin clumps), and necrotic Sertoli cells (characterized with marginated chromatins along the nuclear membrane, ruptured vesicles within the MNB, some swollen and ruptured cell organelles, e.g. mitochondria) could be identified. Conclusively, ultrastructurally the treatment with MEHP at low concentration tends to lead spermatogenic and Sertoli cells to apoptosis, whereas that at high concentration tends to lead spermatogenic and Sertoli cells to necrosis. Thus, the testicular tissue culture is advantageous for screening testicular toxicity of chemicals.