Pharmacokinetic dose-deceleration study in evidence-based medical pharmacovigilance evaluation of anti-asthmatic aerosolised levosalbutamol, and qualitative pharmacogenomic association analysis between adrb2 genetic polymorphisms and β2sympathomimetic mec

Introduction: Levosalbutamol is the purified enantiomer of mixed dextro and levo-rotatory racemic salbutamol, that has a quite high affinity for the β2 receptor. Occupation of β2 receptors by levosalbutamol causes the activation of the Gs-adenylyl cyclase-cAMP-PKA pathway, resulting in phosphorylative events, leading to bronchial smooth muscle relaxation.
Objectives: The objective of this mixed method clinical research was a pharmacokinetic dose-deceleration studyin the evidence-based medical pharmacovigilance evaluation of anti-asthmatic aerosolised levosalbutamol, and qualitative pharmacogenomic association analysis between ADRB2 genetic single nucleotide polymorphisms and β2 sympathomimetic mechanisms.
Methods: 52 global patients, with mild to early moderate asthma, were prescribed the inhalation treatment of levosalbutamol 50mcg per actuation, with a metered dose inhaler, 2 puffs in each nostril, once in the early morning, and once in the early evening, for 1 month, and then, 2 puffs in each nostril, once in the early evening, for the next 1.5 months. After each levosalbutamol inhalation dose, the patients were monitored for 24 hours, for the occurrence of any adverse effect, like headache, tremor, irritation in the oral cavity and palpitation, with Adverse Event Case Report Forms, on 0, 3, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84, 98, 112, and further follow-ups. The patient findings were recorded and statistically analysed. A qualitative pharmacogenomic analysis of ADRB2 genetic single nucleotide polymorphisms association with β2 sympathomimetic mechanisms, was also conducted, with global epigenetic considerations.
Results: There were no occurrence of any adverse drug reaction with 50 mcg levosalbutamol (2 puffs in each nostril BD) and 50 mcg levosalbutamol (2 puffs in each nostril OD) inhalation treatment. The adverse effects of levosalbutamol were not statistically significant; and the stepwise dose decrease of aerosol inhalation of levosalbutamol, were equally safe and tolerable. The pharmacogenomic analysis showed a reasonably substantial association between ADRB2 genetic polymorphisms and β2 sympathomimetic mechanisms.
Conclusions: This safety evaluation study concluded thatanti-asthmatic levosalbutamol aerosol inhalation was safe and tolerable, during the stepwise dose deceleration, with substantial association with ADRB2 genetic polymorphisms.