Previously adverse effects i e fatigue

Previously, adverse effects, i.e. fatigue, nausea, palpitations, headache, dizziness and tremor have been reported for rac-bambuterol (Holstein-Rathlou et al., 1986). It has been suggested R-bambuterol has less cardiac inotropic and chronotropic effects than rac-BMB in animals (Cheng and Tan, 2009). In this study, R-bambuterol administered either as single (10mg) or as multiple doses (5mg/daily) was well tolerated since the lower dose used compared to previous studies (10mg/daily versus 20mg daily). Several studies suggested associations between the regular use of β2-agonist and non-fatal ischemic heart disease (Martin et al., 1998) or hiv protease inhibitors death (Cazzola and Matera, 2007). Based on our findings, these adverse effects may be reduced by using R-bambuterol enantiomer which requires only one half of the dose of rac-bambuterol while limiting the possible non-target effects of S-bambuterol. FlorÉN et al. (1997) reported that rac-bambuterol treatment significantly increases the level of HDL-C, but not significantly change the level of LDL-C. The effect was different from our findings, possibly due to the different experimental settings and the rac-bambuterol administrated. In the previous study, the treatment period was 6–8weeks, whereas in this study the dosing period of R-bambuterol was only one to seven days. Also, the previous study was conducted among patients with hyperlipidemia, who were also at older age (mean age of 59.3years). More importantly, R-bambuterol and S-bambuterol might have different or even contradicting biological effects, which have been observed for other racemic drugs (Caner et al., 2004). Nevertheless, the approximately 15% LDL-C lowering and the marginal ApoA1/ApoB increasing effects of R-bambuterol within a short-term treatment observed in this study is noteworthy. The lipid-lowering effect of R-bambuterol was likely different from that of fibrates and niacin, which also effectively reduced plasma TG levels (Bruckert et al., 2011; Fabbrini et al., 2010). A higher LDL-C/ApoB ratio indicates an increase in the LDL particle size. Unlike statins and fibrates (Watts et al., 2006; Ballantyne et al., 2008), the administration of R-bambuterol did not significantly alter the LDL-C/ApoB ratio (Fig. 4). In addition, oral administration of R-bambuterol in this study did not significantly alter the plasma concentration of glucose or potassium (data not shown), which were found in previous clinic studies when orally administering Rac-bambuterol and other racemic β2-agonists such as albuterol.
Author Contributions
Disclosures
Sources of Funding This work was partially supported by the Major Science and Technology Project of Guangdong Province, China (Grant No.: 2012A080204001). The following are the supplementary data related to this article.