Pharmacokinetics of a novel amoxicillin/colistin suspension after intramuscular administration in pigs

Abstract

An amoxicillin (AMO) or colistin (COS) oil suspension was developed and corresponding pharmacokinetics studies were conducted in pigs after i.m. injection. The combination product is a white- to cream-colored oil suspension which is easy to be re-dispersed. Settling volume ratio, syringeability and flowability of the product is well consistent with the technical standards set by the Ministry of Agriculture of People's Republic of China. Two studies were conducted to investigate the pharmacokinetics of the combination product in swine. First, the pharmacokinetics of the combination product was compared with those of the same products merely removing either AMO or COS. No significant change in the major pharmacokinetic parameters (C(max) , T(max) , MRT, t(1/2λ) , AUC and AUMC) was observed when either component was removed from the combination product, indicating that AMO and COS do not interfere with each other in their absorption and distribution in the tissue when used as a combination. Second, the pharmacokinetics of the combination product was compared with that of their respective single products. It was found that the apparent elimination half-lives (t(1/2λ) ) of AMO and COS in combination product were 6.38 and 8.09 h, which were 2.40 and 2.38 times longer than the single products, respectively. Thus, the novel AMO/COS suspension extended significantly the half-life of both drugs to maintain a longer drug residence time in pigs when compared to their single products.

Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action, Microbial Resistance Emergence, and One Health Perspectives

“…Unlike for human medicine, only a few studies have been conducted in pigs to evaluate the PK of colistin following oral (Guyonnet et al, 2010; Rhouma et al, 2015, 2016b) or intramuscular (IM) administration (Lin et al, 2005; Tang et al, 2009; He et al, 2011; Table 1 ). These studies were performed using CS, since this is the only form of colistin approved in swine medicine, and were conducted in healthy pigs.…”

“…However, there are some commercial formulations where CS is associated with others antimicrobial agents, mostly with β-lactam antibiotics (He et al, 2011) such as ampicillin or amoxicillin ( Table 3 ). In fact, it has been shown that the combination of amoxicillin with colistin has a synergy and additive affect in vitro against pathogenic E. coli of avian origin, without antagonism between the two antibiotics (Hamouda et al, 2011).…”

Pharmacokinetics and relative bioavailability of meloxicam oil suspension in pigs after intramuscular administration

“…In the meantime, it has the advantage of sustained‐release so that prolongs the action time of the drug and reduces the frequency of drug delivery, determining the feasibility of the dosage form in the veterinary clinic. Amoxicillin and ceftiofur hydrochloride oil suspension are typical representations of it (He et al, ; Hibbard et al, ; Tang et al, ; Xiong et al, ).…”

Pharmacokinetics and relative bioavailability of an oral amoxicillin-apramycin combination in pigs

“…Unfortunately, AMO monotherapy has proven to be less effective in recent times due to the wide-spread occurrence of multi-drug resistant (MDR) bacteria [4, 5]. Antibiotic combination therapy is a far more effective approach for combating MDR pathogens and preventing the emergence of resistance commonly seen with monotherapy [4, 6]. A very effective therapeutic approach is to combine antibiotics with different modes of action.…”

“…A very effective therapeutic approach is to combine antibiotics with different modes of action. For example, it has demonstrated that the combination AMO (a cell wall synthesis inhibitor) with antibiotics that act on different cellular targets such as gentamicin [4], colistin [6] and ceftriaxone [7], has been shown to have a marked synergistic effect. Intuitively, we took the novel approach to combine AMO with apramycin (APR), an aminoglycoside which displays a unique bicyclic sugar moiety and a 4-monosubstituted 2-deoxystreptamine ring [8].…”