Serum theophylline concentration levels and preventative effects on exercise-induced asthma

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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The Relationship between Serum Theophylline Concentration and Urine Theophylline Metabolites in Asthmatic Children-A Comparison between Two Groups with Unchanged and Decreased Plasma Concentration.

Japanese Journal of Pediatric Pulmonology ◽

10.5701/jjpp.9.91 ◽

1998 ◽

Vol 9 (2) ◽

pp. 91-96

Author(s):

Akiko Yamaguchi ◽

Yuji Okano ◽

Tomonori Tateishi ◽

Yasushi Koitabashi

Keyword(s):

Plasma Concentration ◽

Theophylline Concentration ◽

Serum Theophylline Concentration ◽

Serum Theophylline ◽

Asthmatic Children ◽

The Relationship

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Management of Theophylline Overdose Patients in the Intensive Care Unit

Anaesthesia and Intensive Care ◽

10.1177/0310057x9202000111 ◽

1992 ◽

Vol 20 (1) ◽

pp. 56-62 ◽

Cited By ~ 18

Author(s):

A. Henderson ◽

D. M. Wright ◽

S. M. Pond

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Muscle Relaxation ◽

Theophylline Concentration ◽

Serum Theophylline Concentration ◽

Serum Theophylline ◽

Release Preparation ◽

Effective Delivery ◽

Grand Mal ◽

Theophylline Poisoning

In a retrospective survey of all adults admitted to the Intensive Care Unit with acute theophylline poisoning over the last five years, we identified 38 patients (6.8% of all admissions for poisoning), two of whom died. Thirty-five (92%) had taken a sustained-release preparation. Eight patients had grand mal seizures and six developed arrhythmias (ventricular fibrillation, 3; atrial fibrillation, 2; supraventricular tachycardia, 1). Severe vomiting was present in 34 (89%) and proved to be a serious obstacle to the administration of enteral charcoal. The vomiting was controlled by intravenous metoclopramide in seventeen patients (50%), but the remaining seventeen required mechanical ventilation with sedation and muscle relaxation for the effective delivery of nasogastric charcoal. Importantly, in nine (24%), the serum theophylline concentration continued to rise despite enteral charcoal. Charcoal haemoperfusion was used in seven (18%). We present an algorithm for the management of severe, acute theophylline poisoning.

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