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.

Pharmacokinetics and bioavailability of doxycycline in ostriches (Struthio camelus) at two different dose rates

A bioavailability and pharmacokinetics study of doxycycline was carried out on 30 healthy ostriches after a single intravenous (IV), intramuscular (IM) and oral dose of 15 mg/kg body weight. The plasma doxycycline concentration was determined by HPLC/UV at 0 (pretreatment), 0.08, 0.25, 0.5 1, 2, 4, 6, 8, 12, 24 and 48 h after administration. The plasma concentration-time curves were examined using non-compartmental methods based on the statistical moment theory for only the higher dose. After IV administration, the elimination half-life (t(1/2beta)), mean residence time (MRT), volume of distribution at the steady-state (V(ss)), volume of distribution (Vd(area)) and total body clearance (Cl(B)) were 7.67 +/- 0.62 h, 6.68 +/- 0.86 h, 0.86 +/- 0.16 l/kg, 1.67 +/- 0.52 l/kg and 2.51 +/- 0.63 ml/min/kg, respectively. After IM and oral dosing, the mean peak plasma concentrations (C(max)) were 1.34 +/- 0.33 and 0.30 +/- 0.04 microgram/ml, respectively, which were achieved at a postadministration time (t(max)) of 0.75 +/- 0.18, 3.03 +/- 0.48 h, respectively. The t(1/2beta), Vd(area) and Cl(B) after IM administration were 25.02 +/- 3.98 h, 23.99 +/- 3.4 l/kg and 12.14 +/- 1.71 ml/min/kg, respectively and 19.25 +/- 2.53 h, 61.49 +/- 7 l/kg and 40.19 +/- 3.79 ml/min/kg after oral administration, respectively. The absolute bioavailability (F) of doxycycline was 5.03 and 17.52% after oral and IM administration, respectively. These results show that the dose data from other animals particularly mammals cannot be extrapolated to ostriches. Therefore, based on these results along with those reported in the literature, further studies on the pharmacokinetic/pharmacodynamic, in vitro minimum inhibitory concentration values and clinical applications of doxycycline in ostriches are required.