Pharmacokinetics and Dosage Regimen of Ceftriaxone in Buffalo Calves

Abstract

The pharmacokinetics and dosage regimen of ceftriaxone were investigated in buffalo calves (n = 6) following a single intravenous administration of ceftriaxone (10 mg/kg). The elimination rate constant was 0.18 +/- 0.01 h(-1) and the elimination half-life was 3.79 +/- 0.09 h. The apparent volume of distribution (Vd(area)) was 1.40 +/- 0.01 L/kg and the total plasma clearance was 0.26 +/- 0.01 L/(kg h). Approximately 43% of total administered dose of ceftriaxone was excreted in urine within 8 h. To maintain a minimum therapeutic concentration of 1 microg/ml, a satisfactory intravenous dosage regimen of ceftriaxone in buffalo calves is 13 mg/kg repeated at 12 h intervals.

Disposition kinetics and urinary excretion of cefpirome after intravenous injection in buffalo calves

“…Comparable values of Cl B were reported for cefpirome in dogs (3.2 ml/kg/min), guineapigs (1.57 ml/kg/min), and humans (1.8 ml/kg/min) following single intravenous injections [11]. Also, similar value of Cl B was reported after intravenous injection of ceftriaxone (0.26 l/kg/h) in buffalo calves [4]. …”

Plasma pharmacokinetics and milk levels of ceftriaxone following single intravenous administration in healthy and endometritic cows

“…In agreement to the present results, lower values of Vd area have been reported for ceftriaxone in ewes (0.28 L.kg −1 ), camel (0.32 L.kg −1 ) and goats (0.28-0.58 L.kg −1 ) after intravenous administration (Goudah et al 2006;Sar et al 2006;Goudah 2008;Tiwari et al 2009). However, large Vd area has also been Cp 0 = plasma drug concentration at time zero of intravenous dosing; α 1 and α 2 = distribution rate constants from central to peripheral compartments; β = elimination rate constant; t 1/2 α 1 and t 1/2 α 2 = distribution half lives of the two distribution phases; t 1/2 β = elimination half life; K 12 , K 13 , K 21 and K 31 = rate constants of drug transfer from central to peripheral compartments and vice-versa; AUC = area under the plasmaconcentration time curve; AUMC = area under the first moment of plasma-concentration time curve; Vd (area) = apparent volume of distribution; Cl B = total body clearance of drug; K el = rate constant for elimination of drug from central compartment; MRT = mean residence time; P/C = ratio of drug present in peripheral to central compartment reported for ceftriaxone in calves (1.91 L.kg −1 ) and buffalo calves (1.4 L.kg −1 ) following intravenous administration (Johal and Srivastava 1999;Dardi et al 2004). The larger Vd area in endometric cows (1.55±0.52 L.kg −1 ) in comparison to that in healthy animals indicated greater distribution of the drug during endometritis.…”

“…On the contrary, lower concentrations of ceftriaxone have been reported in ewes (0.22 μg.ml −1 ) at 10 h following intravenous dose of 10 mg.kg −1 and in goats (33.3 μg.ml −1 ) at 3 h after intravenous dose of 50 mg.kg −1 (Goudah et al 2006;Sar et al 2006). Taking 6 h as a dosage interval (τ), with a minimum therapeutic plasma level (Cp min ∝ ) of 0.5 μg.ml −1 and using the values of β and Vd area of healthy cows from Table 1, the priming and maintenance doses of ceftriaxone were calculated as 10.7 and 10.4 mg.kg −1 , respectively The dosage interval was shorter than 12 and 24 h dosing interval suggested for the same doses of ceftriaxone in calves and buffalo calves, respectively (Johal and Srivastava 1999;Dardi et al 2004). The ultimate objective of the pharmacokinetic study was to determine an appropriate intravenous dosage regimen of ceftriaxone for cows suffering from endometritis.…”

“…The presence of drug residues in milk may have public health implications, and is perceived by consumers as undesirable, therefore knowledge about the penetration of ceftriaxone from blood to milk is worth consideration (Goudah et al 2006). Disposition kinetics of ceftriaxone has been conducted in calves (Johal and Srivastava 1999;Soback and Ziv 1988), buffalo calves (Dardi et al 2004(Dardi et al , 2005(Dardi et al , 2007Gohil et al 2009), sheep (Guerrini et al 1988;Goudah et al 2006), goats (Sar et al 2006;Tiwari et al 2009) and camel (Goudah 2008). However, information on the pharmacokinetics of ceftriaxone in cattle species under endometritic condition is meager.…”

Potential of a polyherbal drug to prevent antimicrobial resistance in bacteria to antibiotics

“…Therefore, it can be expected that the polyherbal drug will enhance excretion of ceftizoxime from milk compartment shortening the persistence of eftizoxime residue in milk after achieving higher concentration for a certain period of time during the late hours following single intravenous dosing of ceftriaxone. Though the pharmacokinetic study of ceftriaxone was conducted in many ruminant species following parenteral administration, e.g., sheep 10 cow calves 11 , crossbred calves 12,13 , buffalo calves 14,15 , lactating goats 3,5,7 and crossbred mastitic cows 6 but disposition study of its active metabolite, e.g., ceftizoxime to determine pharmacokinetic parameters in milk following intravenous dosing of the parent ceftriaxone was not done. Dosing interval of antibacterial drug in mastitis or other bacterial infections also should be based on maintenance of therapeutic concentration of its active metabolite at the site of infection e.g., mammary gland/milk in mastitis particularly when the metabolite is the major active metabolite of the parent drug and when the active metabolite, not the parent drug excretes through milk at a higher rate.…”