Theophylline disposition in Korean patients with congestive heart failure

OBJECTIVE: This study proposed to determine the systemic disposition of theophylline in Korean adult patients during decompensated congestive heart failure compared with disposition after recovery. DESIGN: An experimental, prospective, self-controlled, nonrandomized design was used. SETTING: The study was performed in a general community hospital located in Pusan, Korea. PATIENTS: Eight nonsmoking elderly Korean patients with decompensated congestive heart failure presenting to the emergency department were included in the study. Consecutive patients who met entrance criteria were selected. All patients completed the study. INTERVENTIONS: A single dose of aminophylline 6 mg/kg was administered by intravenous infusion over 30 minutes. Standard methods of congestive heart failure therapy were used in each patient, including bed rest, restriction of sodium, and drug therapy including digoxin. After compensation of congestive heart failure was achieved, the theophylline infusion was repeated. OUTCOME MEASURES: Serum theophylline concentrations were measured at 2, 6, 12, and 18 hours after completion of the dose at baseline and following treatment. RESULTS: A clinically and statistically significant improvement in mean theophylline total body clearance was demonstrated following treatment (from 21.7 +/- 2.8 to 43.4 +/- 4.7 mL/kg/h [mean +/- SEM]; p < 0.01). Comparison of these results with a computer model based on literature averages of peoples of all nationalities showed significant underprediction of theophylline clearance both before (p < 0.05) and after (p < 0.01) treatment. The theophylline elimination half-life prior to treatment was 18.2 +/- 2.2 hours and decreased to 9.1 +/- 0.8 hours following treatment (p < 0.01). There was no statistical difference between the computer-model predicted initial theophylline half-life and the measured value, but the model significantly underpredicted the improvement following treatment. CONCLUSIONS: The improvement in theophylline clearance demonstrated in this study appears to be greater than that reported for Western patients. This has practical application to the calculation of appropriate theophylline maintenance dosage regimens in Korean patients with cardiac failure. These data support the need for consideration of racial differences in individualizing dosage regimens. We suggest that all kinetic models, whether software supported or not, should consider incorporating ethnic origin as a demographic factor that helps select the proper model for individual patients.

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