Aminophylline (DB01223): A Comprehensive Pharmacological and Clinical Monograph

Introduction

Aminophylline is a pharmaceutical compound that has occupied a significant, albeit evolving, position in therapeutic medicine for decades. It is not a single active agent but rather a 2:1 complex of the bronchodilator theophylline and the solubilizing agent ethylenediamine.[1] This chemical union was engineered to overcome the poor water solubility of theophylline, thereby enabling its formulation for intravenous administration in acute clinical settings. Consequently, the clinical identity and pharmacological profile of aminophylline are fundamentally inseparable from those of its active moiety, theophylline.

Historically, aminophylline was a cornerstone in the management of bronchospastic diseases, serving as a first-line therapy for acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD).[4] However, its therapeutic dominance has waned considerably with the advent of safer and more effective agents, such as selective beta-2 adrenergic agonists and inhaled corticosteroids. The primary factors driving this shift in clinical practice are aminophylline's narrow therapeutic index, its highly variable and unpredictable pharmacokinetic profile, and a substantial potential for severe, life-threatening toxicity.[5]

This monograph will provide an exhaustive analysis of aminophylline, arguing that a thorough and nuanced understanding of its complex pharmacology, highly variable pharmacokinetics, and significant potential for toxicity is essential for its safe and effective use in its remaining niche indications. While its role in respiratory medicine has been largely superseded, its unique mechanisms of action continue to afford it a place in specific clinical scenarios, demanding a high level of expertise from the prescribing clinician.

Section 1: Chemical Profile and Formulation

1.1. Identification and Nomenclature