Rapid rise in serum theophylline concentration after overdose with sustained release theophylline

It has been known for some time that after the ingestion of a large quantity of sustained-release aminophylline tablets, a secondary rise in theophylline concentration may occur (Connell et al., 1982). This has, in the past, been ascribed variously to continued absorption from the sustained release formulation (Struthers et al., 1982) or to redistribution of the drug after charcoal haemoperfusion (Connell et al. , 1982). This case demonstrates that Phyllocontin S-R tablets may cause a compacted mass in the stomach, which may become resistant to gastric lavage, and thus become a potential source of a sudden secondary rise in theophylline concentration.

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Relationship of formulation and dosing interval to fluctuation of serum theophylline concentration in children with chronic asthma

The Journal of Pediatrics ◽

10.1016/s0022-3476(81)80982-1 ◽

1981 ◽

Vol 99 (1) ◽

pp. 145-152 ◽

Cited By ~ 84

Author(s):

Miles Weinberger ◽

Leslie Hendeles ◽

Lai Wong ◽

Leigh Vaughan

Keyword(s):

Chronic Asthma ◽

Theophylline Concentration ◽

Serum Theophylline Concentration ◽

Serum Theophylline ◽

Dosing Interval ◽

Relationship Of

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Clinafloxacin-Theophylline Drug Interaction

Annals of Pharmacotherapy ◽

10.1177/106002809502900407 ◽

1995 ◽

Vol 29 (4) ◽

pp. 378-380 ◽

Cited By ~ 8

Author(s):

Paul R Matuschka ◽

Richard S Vissing

Keyword(s):

Drug Interaction ◽

Pharmacokinetic Interaction ◽

Hepatic Metabolism ◽

Chronic Obstructive ◽

Serum Concentrations ◽

Theophylline Concentration ◽

Serum Theophylline Concentration ◽

Serum Theophylline ◽

Obstructive Pulmonary Disease ◽

The Right

Objective: To report an apparent pharmacokinetic interaction between clinafloxacin and theophylline in a patient with chronic obstructive pulmonary disease (COPD). Case Summary: A patient with a history of COPD was admitted for a fracture of the right femoral neck. Admission medications included extended-release theophylline 400 mg bid. The initial serum theophylline concentration was 81.03 µmol/L (normal 55—110). A subsequent concentration was subtherapeutic (46.62 µmol/L) and the theophylline dosage was increased to 300 mg tid. Therapeutic steady-state concentrations were achieved. The patient later developed pneumonia and was enrolled in a study of nosocomial acquired pneumonia involving clinafloxacin versus ceftazidime. He was randomized to receive clinafloxacin 200 mg iv ql2h. After clinafloxacin therapy was initiated, the serum theophylline concentration increased into the toxic range (155.96 µmol/L). Theophylline administration was held for 2 doses and the dosage then reduced to 200 mg tid. Serum concentrations decreased to within the therapeutic range. Discussion: The fluoroquinolones have been shown to interact with the hepatic metabolism of theophylline and increase serum theophylline concentrations. The quinolone metabolite, 4-oxo-quinolone, inhibits the N-demethylation of theophylline, leading to a decrease in the clearance of theophylline. The resultant rise in theophylline concentrations corresponds with the decrease in clearance and possible toxicity. In our patient, careful monitoring of theophylline concentrations and dosage adjustments resulted in the restoration of therapeutic serum concentrations. Conclusions: The observation of this drug interaction between clinafloxacin and theophylline suggests a need for prudent monitoring of theophylline concentrations. Dosage adjustments may be warranted when this combination of medications is used. Such action may prevent significant toxicities and prolonged hospitalization. Further controlled clinical trials in healthy volunteers are needed to substantiate the interaction between clinafloxacin and theophylline.

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