Theophylline metabolic conversion

Figure 2. Qualitative and quantitative aspects of the metabolic conversion of theophylline by liver microsomal enzymes...

Moracizine modestly increases theophylline clearance, although conversely animal data suggest that moracizine inhibits theophylline metabolism. 

The plasma clearance of theophylline varies widely. Theophylline is metabolized by the liver, so typical doses may lead to toxic concentrations of the drug in patients with liver disease. Conversely, clearance may be increased through the induction of hepatic enzymes by cigarette smoking or by changes in diet. In normal adults, the mean plasma clearance is 0.69 mL/kg/min. Children clear theophylline faster than adults (1-1.5 mL/kg/min). Neonates and young infants have the slowest clearance (see Chapter 59). Even when maintenance doses are altered to correct for the above factors, plasma concentrations vary widely. 

Formation of sulfate esters is one of the metabolic conjugation reactions (phase II reactions, see Chapter 31). Sulfates of estradiol, glucose, menadiol, and hydro-xyethyl-theophylline have been prepared (Fig. 36.9). As a rule sulfuric acid esters, compared with their phosphoric analogues, are resistant to enzymatic hydrolysis in and their conversion to the parent drug is questionable. 

Uncertain. Allopurinol, a xanthine oxidase inhibitor, can block the conversion of methylxanthine to methylurie aeid, but this had no effeet on theophylline levels in two studies. One suggestion is that allopurinol inhibits the oxidative metabolism of theophylline by the liver. ... 

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