Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs

Abstract

This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.

Inflammatory mediator modulation by Short- and Long-Acting β2 Agonists in Induced Bronchial Asthma in Rats

“…Animals received a mixture of 1mg/kg ovalbumin (OVA)/100mg aluminium hydroxide (Al(OH)3 suspended in 1ml of sterile normal saline (0.9% sodium chloride; purchased from Otsuka, Japan) I.P once on day 1 of the experiment (Careau et al, 2002). Three weeks after immunization, animals were treated with either oral salbutamol 2mg/kg (GlaxoSmithKline, UK), bambuterol 10mg/kg (AstraZeneca, Sweden), or prednisolone 3mg/kg (Sanofi, Egypt) (Guan et al, 2015;Hirano et al, 2011;Uzkeser et al, 2012). As well, different combinations were as described below.…”