Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration

Abstract

The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two-compartment open model. Mean plasma elimination-rate constant (beta) and clearance (ClB) for ticarcillin were significantly less (P less than 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P less than 0.05), in the foals at 3 days compared with 28 days of age. This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3-day-old foals. The mean elimination rate constant for clavulanate was significantly less (P less than 0.01) at 3 days than at 28 days of age. Values of the major kinetic terms describing the disposition of ticarcillin after i.m. administration to five 3-day-old foals were not significantly different from values of these parameters in the same foals at 28 days of age. After i.m. administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P less than 0.01), and the elimination-rate constant (kd) for clavulanate was significantly less (P less than 0.01), in 3-day-old foals than in 28-day-old foals. The bioavailabilities of ticarcillin and clavulanate after i.m. administration in 3-day-old foals were 100% and 88.3%, respectively, and in 28-day-old foals were 100% and 27.4%, respectively. Mean plasma ticarcillin concentrations exceeded 16 micrograms/ml for a longer period after i.m. administration of the drug combination than after i.v. administration to foals of both age groups. By virtue of the frequency of administration required and the painful response elicited by i.m. injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC less than or equal to 16 micrograms/ml), it should be administered i.v. four times daily.

Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and oral administration in goats

“…The time to reach peak concentration (tmax) reflects the rate of absorption, whereas the peak concentration (Cmax) is affected by the rate and extent of absorption. A peak plasma concentration of 10.71 mg/1 of amoxicillin was reached at 1.93 h (tmax-tlag) and of 5.75 mg/1 of clavulanic acid at 1.60 h. The tmax values obtained in the present study indicates rapid absorption and is similar to the value reported for amoxicillin in mares of 1.5 h but the mean peak concentration was lower (2.73 mg/I) (30). Such poor absorption and the low peak plasma concentration of amoxicillin in goats were in contrast to the results of studies with dogs and humans (12,13).…”

“…In sheep, however, the bioavailability of ampicillin after oral administration is much lower, namely 6.94% (2). In the present study, the biovavailability of amoxicillin was 27%, similar to the data reported for pre-ruminant veal calves (29% and 32% when given with and without milk, respectively) (35), but higher than those reported for starved horses (5%) (9) and mares (10.46%) (30). No data on the oral bioavailability of clavulanic acid in domestic animals are available.…”

“…In the first phase the mixture was injected into the left jugular vein and blood samples (5 ml) were collected from the contralateral jugular vein into heparinized Vacutainer tubes at 3, 6, 9, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, and 240 minutes after administration. In the second phase the mixture was administered intraruminally by a tube and the blood samples were collected at 30,45,60,75,90,120,150,180,210,240, 300, 360, 420, 480, 540, 600 and 660 minutes after administration. The samples were centrifuged for 15 minutes at 1500 g and the plasma taken and stored 1 day at -40°C pending assay.…”

Pharmacokinetic – Pharmacodynamic Considerations for Bovine Mastitis Treatment

“…Since then AMX disposition was studied after its administration by different routes in production animals (Archimbault et al, 1981;, Nouws et al, 1986, Wilson et al, 1988. According to Erskine et al (2002) We performed some studies with the objective of evaluating the PK behavior of AMX trihydrate in serum and milk after its IM administration at therapeutic dose in healthy lactating cows (Mestorino et al, 1997) (Fig.…”

Bioequivalence study of two oral amoxicillin formulations (Biocillin® and Atcomox 87%®) in broiler chickens

“…The pharmacokinetics of amoxicillin in the chicken followed a two-compartment open model in view of the bi-exponential decline of plasma amoxicillin concentrations; this kinetic disposition was similar to that described previously in man, cows, mares, horses, dogs, and sheep and goats. [13][14][15][16][17][18] Following intravenous administration, the disappearance of the drug from the plasma of chickens was characterized by an initial rapid distribution phase (t0.5α) 0.22 h for both groups; followed by a slower elimination phase (t0.5β) 8.05 and 6.71 h for both groups, respectively. The results indicate that amoxicillin distributed more quickly after intravenous dosing.…”