Relatively higher dose of theophylline is required to attain therapeutic plasma concentration in
**Core Concept**
Theophylline is a methylxanthine derivative used in the management of chronic obstructive pulmonary disease (COPD) and asthma, primarily through its bronchodilatory effect. The therapeutic plasma concentration of theophylline is narrow, and achieving this concentration is crucial for its efficacy and minimizing toxicity.
**Why the Correct Answer is Right**
The relatively higher dose of theophylline required to attain therapeutic plasma concentration is due to its extensive first-pass metabolism by the liver enzyme cytochrome P450 1A2 (CYP1A2). This enzyme is responsible for metabolizing theophylline to its inactive metabolites. In individuals with higher CYP1A2 activity, more theophylline is metabolized, necessitating a higher dose to achieve therapeutic levels.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect as theophylline's pharmacokinetics is not significantly affected by renal function. Theophylline is primarily excreted in the urine, but its clearance is not dependent on renal function.
**Option B:** This option is incorrect as theophylline is not significantly affected by age in terms of its metabolism. Theophylline's clearance is relatively constant across different age groups, and dose adjustments are not typically necessary based on age alone.
**Option C:** This option is incorrect as theophylline's metabolism is not significantly affected by smoking status. While smoking can induce CYP1A2, the effect on theophylline's metabolism is not as pronounced as other factors.
**Clinical Pearl / High-Yield Fact**
It is essential to monitor theophylline plasma concentrations regularly, especially in patients with impaired liver function or those taking medications that induce or inhibit CYP1A2.
**Correct Answer:** C. Patients with cirrhosis, as the liver's impaired ability to metabolize theophylline leads to a higher required dose to attain therapeutic plasma concentrations.