Serum concentration and cardiovascular effects of salbutamol after oral and rectal administration in healthy volunteers

Abstract

In order to evaluate rectal administration of salbutamol (SB), five healthy volunteers were dosed orally and rectally with racemic SB (0.1 mg/kg) solution. Compared with the oral SB, the rectal SB gave significantly higher serum SB concentration immediately after dosing but slightly lower levels in the elimination phase. The Cmax following rectal administration was 17.9 ng/ml (17.0 ng/ml for oral administration), the tmax 0.67 h (1.5 h for oral administration) and the AUC 98.2 ng/ml/h (100 ng/ml/h for oral administration). Heart rate also rose more rapidly to a maximum of 70% above baseline values after rectal dosing. The rate continued to be twice larger than after oral dosing for up to 5 h. The concentration versus response curves indicated that rectal SB was more effective than oral SB at increasing heart rate at the same SB concentration in serum. A plausible explanation for this phenomenon might be a difference in the stereo-selective first-pass metabolism of the two enantiomers. Therefore, the rectal dose of SB administered as a suppository for prophylactic treatment of asthma should be lower than that used orally.

“In‐House” Data on the Outside—A Mobile Health Approach

“…The magnitude of change was comparable to previously reported results. [13][14][15] The changes in SBP and DBP at 3 hours postdose relative to baseline after bisoprolol and salbutamol administration did not generally differ from the no-treatment group, as measured via the A&D UA-767PBT-Ci device ( Table 3). This was aligned with previously reported results for bisoprolol and salbutamol.…”

Phthalazin-1(2H)-one as a remarkable scaffold in drug discovery

“…Thus, some TXA 2 synthetase inhibitors were marketed in Japan for treatment of bronchial asthma in adults reducing the need for concomitant steroid therapy [76].…”

“…Bronchial asthma is a lung disease characterized by airway obstruction, inflammation and hyperresponsiveness [76]. In the traditional treatment for bronchial asthma two different types of drugs, bronchodilators, such as β 2 -agonists and xanthine derivatives, to inhibit the airway obstruction process and steroidal anti-inflammatory drugs to control the airway inflammation and prevent their hyperresponsiveness are involved [77].…”

Stereoselectivity in drug metabolism

“…Furthermore, the degree of stereoselectivity was highly dependent on the route of administration, with the lowest concentration of (R)-albuterol observed after oral administration. The observed oral bioavailability values of (R)-and (S)-albuterol were 9.4 and 68.7%, respectively, a significant stereoselectivity in oral bioavailability due to the substantial enantioselective metabolism on (R)-albuterol [37][38][39][40].…”