J Vet Sci.  2013 Dec;14(4):395-403. 10.4142/jvs.2013.14.4.395.

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

• Soliman AM
• Abu-Basha
• Youssef SA
• Amer AM
• Murphy PA
• Hauck CC
• Gehring R
• Hsu WH

• KMID: 1712305
• DOI: http://doi.org/10.4142/jvs.2013.14.4.395

Abstract

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.

Keyword

amoxicillin; bioavailability; disposition; lead intoxication; pharmacokinetics

MeSH Terms

Amoxicillin/blood/*pharmacokinetics/urine
Animals
Anti-Bacterial Agents/blood/*pharmacokinetics/urine
Area Under Curve
Chromatography, High Pressure Liquid/veterinary
Goat Diseases/*chemically induced/metabolism
Goats
Half-Life
Injections, Intramuscular/veterinary
Injections, Intravenous/veterinary
Lead Poisoning/etiology/metabolism/*veterinary
Male
Amoxicillin
Anti-Bacterial Agents

Figure

• 

  Fig. 1 Ratio (R/F) of the reactivated and free δ-aminolevulinic acid dehydratase (δ-ALAD) in the blood of control and lead-intoxicated goats. The four lead-intoxicated goats received 10 mg/kg body weight/day of lead for 10 weeks. Serum δ-ALAD activity was measured every 2 weeks for 10 weeks. Another five goats served as controls. The R/F ratio significantly increased over time in the lead-intoxicated goats by the addition of glutathione that reactivated the enzyme through chelation. Values are presented as the mean ± SE. *p < 0.05 vs. the control at the corresponding time point.

• 

  Fig. 2 Changes in serum concentrations of alanine aminotransferase (ALT; A), γ-glutamyl transferase (GGT; B), and blood urea nitrogen (BUN; C) in control and lead-intoxicated goats. The four lead-intoxicated goats received 10 mg/kg bw/day of lead for 10 weeks. The serum ALT, GGT, and BUN concentrations were measured every 2 weeks for 10 weeks. Another five goats served as controls. A significant increase in serum concentrations of ALT, GGT, and BUN in the lead-intoxicated goats indicated damage to the liver and kidney. Values are expressed as the mean ± SE. *p < 0.05 vs. the control at the corresponding time points.

• 

  Fig. 3 The serum concentration-time profile of amoxicillin (10 mg/kg bw) after IV administration in control and lead-intoxicated goats. The four lead-intoxicated goats received 10 mg/kg bw/day of lead for 10 weeks. Another five goats served as controls. Amoxicillin was administered after 10 weeks of lead administration. Data are presented as the mean ± SE. *p < 0.05 vs. the control at the corresponding time point.

• 

  Fig. 4 The serum concentration-time profile of amoxicillin (10 mg/kg bw) after IM administration in control and lead-intoxicated goats. The four lead-intoxicated goats received 10 mg/kg bw/day of lead for 10 weeks. Another five goats served as controls. Amoxicillin was administered IM 12 weeks after the onset of lead administration (2 weeks after the IV amoxicillin experiment). Values are presented as the mean ± SE. *p < 0.05 vs. the control at the corresponding time points.

• 

  Fig. 5 Average input rates of amoxicillin and cumulative input for lead-intoxicated (solid line) and control (dashed line) goats. (A) Average input rates and (B) average cumulative input over time. These data were calculated based on extravascular data of the IM amoxicillin experiment with the deconvolution analysis. More rapid absorption and disposition of the amoxicillin was observed in the lead-intoxicated animals compared to the controls.

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