Disposition and oral bioavailability of amoxicillin and clavulanic acid in pigs

Abstract

The pharmacokinetic properties of amoxicillin and clavulanic acid were studied in healthy, fasted pigs after single intravenous (i.v.) and oral (p.o.) dosage of 20 mg/kg of amoxicillin and 5 mg/kg of clavulanic acid. The plasma concentrations of the drugs were determined by validated high-performance liquid chromatographic methods and the pharmacokinetic parameters were calculated by compartmental and noncompartmental analyses. After i.v. administration of the two drugs, plasma concentration-time curves were best described by a three-compartmental open model for amoxicillin and a two-compartmental open model for clavulanic acid. Amoxicillin (with a t(1/2 gamma) = 1.03 h and a clearance of 0.58 L/h.kg) and clavulanic acid (with a t(1/2 beta) of 0.74 h and a clearance of 0.41 L/h.kg) were both rapidly eliminated from plasma. Both drugs had apparently the same volume of distribution of 0.34 L/kg. After p.o. administration of the two drugs, a noncompartmental model was used. Elimination half-lives of amoxicillin and clavulanic acid were not significantly different, i.e. 0.73 and 0.67 h respectively. The mean maximal plasma concentrations of amoxicillin and clavulanic acid were 3.14 and 2.42 mg/L, and these were reached after 1.19 and 0.88 h respectively. The mean p.o. bioavailability was found to be 22.8% for amoxicillin and 44.7% for clavulanic acid.

Pharmacokinetics of the amoxicillin–clavulanic acid combination after intravenous and oral administration in cats

“…The V z of AMX calculated here was relatively higher than those reported in dogs (0.312 L/kg; Kung & Wanner, ) and pigs (0.55 L/kg; Agerso & Friis, ). The present V ss values of AMX and CLV were also wider than those, with the same values of 0.34 L/kg, reported in pigs after intravenous administration of the combination of AMX‐CLV (Reyns et al, ).…”

“…The terminal half‐life ( t 1/2λz ) was determined as 1.26 and 0.69 hr for AMX and CLV, respectively (Tables and ), and the total body clearance was estimated as 0.453 and 0.921 L hr −1 kg −1 (Tables and ), respectively. The clearance of AMX reported here was close to that in pigs ranging from 0.37 to 0.59 L hr −1 kg −1 (Agerso & Friis, ; Reyns et al, ); however, a relatively slower elimination was reported in dogs with a steady‐state rate of clearance of 0.204 L hr −1 kg −1 (Kung & Wanner, ). After oral combination administration, the t 1/2λz of AMX was estimated to be 1.25 hr (Table ), which was very close to that value (1.26 hr) previously reported in cats after oral dosing of AMX alone (Chicoine et al, ).…”

The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid

“…Atomic coordinates are taken from the code 1AO6 [82] of the Protein Data Bank. concentration levels approximately 1 h after oral administration, with similar time-concentration profiles [75], low levels of serum protein binding with approximately 70% of the drug remaining free in serum (as described in Vademecum) and a mean bioavailability of 22.8% [76]. A great variability in the clearance of both AX and CLV has been found in critically ill patients treated with AX-CLV [77].…”

Oral bioavailability and pharmacokinetic profile of the amoxicillin–clavulanic acid combination after intravenous and oral administration in Turkeys

“…, 2009). Oral bioavailability and pharmacokinetic behavior of the combination was investigated in pigs (Reyns et al. , 2007), goats (Carceles et al.…”