Chemotherapy and pharmacokinetics of some antimicrobial agents in healthy dwarf goats and those infected with Ehrlichia phagocytophila (tick-borne fever)

In this investigation the pharmacokinetics of three commonly used antibiotics, ampicillin trihydrate (10 mg/kg), gentamicin sulphate (3 mg/kg) and oxytetracycline hydrochloride (5 mg/kg), given intravenously, were each studied in five Nubian goats and five desert sheep. The pharmacokinetic parameters were described by a two-compartment open model. The results indicated that there were significant differences between the two species in some kinetic parameters of ampicillin and oxytetracycline but not gentamicin. Ampicillin elimination half life (t[1/2beta]) in goats (1.20 h) was shorter than that in sheep (2.48 h), and its clearance (Cl) significantly higher in goats (2921 mL/h x kg) compared to sheep (262 mL/h x kg) (P < 0.01). Ampicillin volume of distribution (Vd[area]) was found to be significantly larger in goats (5673 mL/kg) than in sheep (992 mL/kg) (P < 0.01). For oxytetracycline, the t(1/2beta) in goats (3.89 h) was significantly shorter than that in sheep (6.30 h) and the Cl value in goats (437 mL/h x kg) was significantly higher than in sheep (281 mL/h x kg). The results suggest that when treating sheep and goats, the pharmacokinetic differences between the two species must be considered in order to optimize the therapeutic doses of ampicillin and oxytetracycline.

Section: Paper 061 Discsupporting

confidence: 67%

Section: Paper 061 Discsupporting

confidence: 64%

Comparative pharmacokinetics of ampicillin trihydrate, gentamicin sulphate and oxytetracycline hydrochloride in Nubian goats and desert sheep

Elsheikh

Osman

Ali

1997

“…In earlier reports, TBF-infected goats has significantly prolonged elimination half-life values for chloramphencol (Anika et al, 1986a), sulphadimidine, and oxytetracycline (Anika et al, 1986b). The greatest changes were observed with sulphadimidine and chloramphenciol where the metabolism of both drugs exhibited marked differences in the healthy and febrile animals (Anika et al, 1986a;Nouws et al, 1986).…”

Section: Effects Of Tick-borne Fever On IV Pharmacokinetics Of Ap Amentioning

confidence: 88%

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats

Knoppert¹,

Nijmeijer²,

Duin³

et al. 1988

Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick-borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (n = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration-time curves for both drugs followed first-order two-compartment decay. For TMP, mean t1/2 beta +/- SEM (h) was 0.84 +/- 0.06 (i.v. control) and 0.90 +/- 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 +/- 0.31 (i.v. control) and 10.28 +/- 0.67 (i.v. infected) were obtained (P less than 0.05). Mean Vd beta +/- SEM values (l/kg) were 3.84 +/- 0.27 (i.v. control) and 4.07 +/- 0.85 (i.v. infected) for TMP (NS) and 7.02 +/- 0.63 vs 9.29 +/- 0.21 (P less than 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P less than 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 +/- 0.06 micrograms/ml and 0.85 +/- 0.17 microgram/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 +/- 0.01 microgram/ml and the maximum was reached after 1.2 +/- 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 +/- 0.02 microgram/ml with Tmax of 22.5 +/- 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.

“…, 1990) suffering from pneumonic pasteurellosis. On the contrary, a significant increase in the half‐life of OTC was observed in goats with tick‐borne fever (Anika et al. , 1986) and in those given E. coli endotoxin (Manna et al.…”

Section: Discussionmentioning

confidence: 99%

Influence of endotoxin on the disposition kinetics and dosage regimens of oxytetracycline in calves

Kumar

Malik

2003

The influence of endotoxin on the disposition kinetics of oxytetracycline (OTC) (10 mg/kg) was investigated in five healthy ruminating male crossbred calves. The serum concentration-time data of OTC before and after endotoxin challenge were best described by a two-compartment open model. Repeated administration of Escherichia coli endotoxin (1 microg/kg, i.v.) at an interval of 12 h up to 48 h produced a clear rise in the body temperature and an increase in the pulse and respiration rates. Endotoxin caused a significant reduction in mean transit time in tissue compartment (MTTT) (P < or = 0.05), mean residence time in the peripheral tissue compartment (MRTT) (P < or = 0.05), mean residence time in the body (MRTB) (P < or = 0.05), elimination half-life (t1/2lambda2) (P < or = 0.05) and distribution space in tissues (VT) (P < or = 0.01) and at steady-state (Vd(ss)) (P < or = 0.01). Endotoxin had no effect on the distribution clearance (ClD), systemic clearance (Cl) and distribution half-life of OTC, while the values of first order rate constant of transfer of drug from tissue to central compartment (K21) and the zero time intercept at terminal phase (C2) were significantly high. The drug dosage regimens to maintain serum OTC concentrations of 0.5, 1, 2, 4, 6 and 8 microg/mL were also determined in febrile and clinically healthy animals.