Pharmacokinetics of ceftazidime administered to lactating and non-lactating goats

Abstract

The aim of this work was to determine the pharmacokinetics of intravenous (iv) and intramuscular (im) ceftazidime administered to lactating (LTG; n = 6) and non-lactating (NLTG; n=6) healthy Creole goats in 2 trials (T1 and T2). During T1 and T2, goats randomly received a single dose of im or iv ceftazidime (10 mg/kg). Serum concentration of iv ceftazidime in NLTG and LTG goats is best described by 2 and 3 compartment models, respectively. The pharmacokinetic parameters of iv and im ceftazidime administered to LTG and NLTG showed statistically significant differences (P<0.05) in the constants (λz, T1 vs T2 [iv] 0.5±0.1 vs 0.3±0.1 /h; T1 vs T2 [im] 0.5±0.2 vs 0.3±0.1 /h) and in the mean times (t1/2, T 1 vs T 2 [iv] 1.6±0.3 vs 2.3±0.6 h; T 1 vs T 2 [im] 1.6±0.7 vs 2.6±0.9 h) of elimination. The bioavailability of ceftazidime in LTG and NLTG was 113.0 ± 17.8 and 96.0 ± 18.0 %, respectively. Ceftazidime concentration in milk at 2 h was: iv = 1.9 ± 0.2 and im = 2.4 ± 0.5 μg/m ; the penetration in milk was iv = 18.3 ± 13.5 and im = 14.3 ± 10.6 %. Ninety-six hours after iv and im administration, residues of the drug were not found in milk. In conclusion, ceftazidime, when administered to goats, showed high concentration times in serum, good penetration into milk and a bioavailability that makes it suitable to be used by the im route

Pharmacokinetic Parameters of Meropenem in the Plasma and Milk of Ewes

“…The capability of Meropenem to penetrate into milk compartment was assessed by penetration ratio which expressed as AUC milk /AUC plasma (37) . Our results about milk penetration ratio of intravenously administered Meropenem were 0.86 which considered good in comparison to other Beta-lactams that administered parentrally in different ruminants; where Ceftriaxone was achieved 0.34 in ewes (38) , Ceftizidime 0.16 in does (39) , Cephacetrile 0.15, Cephapirin 0.18, Penicillin G 0.2, Cloxacillin 0.26, Ampicillin 0.26 in cows (40) and Amoxicillin 0.48 in cows (41) . Our assumption to explain such high penetration ratio might be due to the used route of administration who primarily ensure even drug distribution to all extravascular compartments, consequently, they accumulate in milk better than other routes and such phenomena is governed by the amount of used dose (42) ; and the physicochemical characteristics of the drug like zwitterionic nature and the small molecular size of the drug who might be enhance Meropenem penetration to the milk compartment in comparison to other Beta-lactams (43) .…”

Plasma disposition of ceftazidime in healthy neonatal foals following intravenous and intramuscular administration

“…The pharmacokinetics of ceftazidime have been evaluated in other species, suggesting a dose range of 10–50 mg/kg (Albarellos et al, 2008; Goudah & Hasabelnaby, 2013; Monfrinotti et al, 2010; Rule et al, 1991, 1996, 2011). Anecdotally, a dosing range of 20–50 mg/kg of ceftazidime every 6–12 h has been utilized for the treatment of septic neonatal foals.…”

“…In other species, ceftazidime has low levels of serum protein binding, is excreted unchanged via glomerular filtration (O'Callaghan et al, 1980), and shares a similar safety profile in azotemic patients when compared to other third‐generation cephalosporins (Meyers, 1985). As pharmacokinetic and pharmacodynamic information has not previously been described in neonatal foals, a wide range of dosages have been extrapolated from other species and used to treat septic foals (Rule et al, 2002; Rule et al, 1996; Rule et al, 1991; Rule et al, 2011). Because ceftazidime is a medically important antibiotic, for which the consequences of resistance have potential effects on both human and animal health, it is critical that a correct dose be established to promote judicious use of this antimicrobial.…”

Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats

“…The MIC90 values of cephalexin against coagulase-positive staphylococci and E. coli were 1.0 μg/ml and 8.0 μg/ml, respectively [59]. But MIC90 value (0.01-0.1 μg/ml) of ceftazidime against E. coli, Salmonella species, Pasteurella haemolytica and P. multocida [45] shows that ceftazidime is more active and efficacious than cephalexin, which can be administered 8 mg/kg i.m. or subcut every 12 or 24 h, respectively [59].…”

“…Although the information on pharmacokinetics of wild goats is rare, allometric scaling can be applied for extrapolation of some parameters including Vd and Cl except T1/2β [58]. Ceftazidime (10 mg/kg) administered to Creole goat showed high serum concentration, good penetration and high bioavailability of the drug [45]. But cephalexin (10 mg/kg) administered (subcut, i.m.…”