Theophylline plasma protein binding

The toxic concentrations for theophylline in neonates have not been well defined, and can vary from infant to infant. Other pharmacokinetic factors, such as low plasma protein binding and limited capacity for excretion could make neonates prone to aminophylline toxicity. Fetuses and neonates can develop theophylline toxicity even with plasma concentrations in the target range, since they can metabolize theophylline to caffeine, adding to the methyl-xanthine load. 

A a Eh X 0 a e Eh P) t=L Use with caution in patients over 50 years oid with kidney or liver faiiure. PO/IV/IM. Little plasma protein binding, little metabolism. Cimetidine increases serum concentrations of many drugs (oral anticoagulants, theophylline, lidocaine, phenytoin, benzodiazepines, nifedipine, propranolol) by inhibiting liver P450 enzymes. May inhibit renal tubular secretion of procainamide. ... 

The percentage of binding to plasma protein is low for caffeine (35%) and theobromine (15 to 25%), but fairly high for theophylline (55 to 67%). This higher binding of theophylline should be considered when it is used as a prescription drug. 

In plasma, a moderate fraction of approximately 40% of theophylline is reversibly bound to plasma proteins. hi patients with hepatic cirrhosis and reduced serum albumin concentration, binding is reduced to 30 to 35%. In full-term neonates, approximately one third of theophylhne is protein bound. Microdialysis investigations revealed theophylline tissue exposures of 55% of serum concentrations in muscle and subcutaneous tissue indicating equihbrium between unbound theophylline concentrations in serum and tissues. ... 

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