Comparative plasma and tissue pharmacokinetics and drug residue profiles of different chemotherapeutants in fowls and rabbits |
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Authors: | T LI GL QIAO GZ HU FD MENG YS QIU XY ZHANG WX GUO HL YIE SF LI SY LI |
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Institution: | Pharmacology and Toxicology Program. Northeast Agricultural University, Harbin 150030, China;*Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, Box 8401, North Carolina State University, Raleigh, NC 27606, USA |
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Abstract: | Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied. Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers. Penicillin (PEN), intramuscularly at 200 000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits. For each drug, 13–18 groups ( n = 5–10 individuals/group) of the dosed animals were killed at different post-dosing times. Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures. Multi-exponential kinetic models were fitted to the observed tissue concentration-time data by applying a non-linear least-squares regression computer program. Tissue half-life, peak tissue concentration, and time of peak tissue concentration were determined. Half-life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6–1.4, 4.7–9.0, 4.5–18.9, 1.8–3.1, 0.9–3.0, 3.4–9.6, 5.0–16.1 and 7.4–12.2 h. The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 μg/g in various tissues ranged from 5.0–11.6. 70.0–110.5. 114.0–179.8, 21.3–30.3,4.1–24.8 and 47.8–84.4 h. Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue. It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs. Knowledge of tissue kinetics is also important in predicting and controlling drug residues in edible tissues of food-producing animals. |
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