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  • Title: [Intravenous theophylline: adaptation of dosage to blood theophylline levels at admission and to clearance].
    Author: Laaban JP, Dupeyron JP, Guyon F, Drieu L, Rochemaure J, Fabiani P.
    Journal: Ann Med Interne (Paris); 1986; 137(5):415-9. PubMed ID: 3813276.
    Abstract:
    Intravenous infusions of aminophylline expose the patient to the risk of overdosage related to the narrow safety margin of the therapeutic concentrations and to the great individual variability of its excretion. The aim of this study was to evaluate a simplified protocol designed to determine the optimal dose of theophylline based on total body clearance. Forty-four patients (average age: 63 years) admitted with decompensation of chronic respiratory failure (N = 33) or with status asthmaticus (N = 11) were studied. Theophylline was administered initially at a constant rate R0 (mg/kg/h) depending on serum theophylline concentrations on admission T0 (mg/l): R0 = 0.75 - 0.75 T0/20. Serum theophylline concentrations were measured at the 6th and 12th hours (T6 and T12) for calculation of clearance (Chiou et al. J. Pharmacokinet. Biopharm., 1978, 6, 135-151) and for adjusting dosage R. After 48 hours of treatment at this infusion rate, serum theophylline was again measured (T48) to check the adjustment of the dosage and recalculate clearance. In 11 patients T0 was greater than 15 mg/l (max = 44) and T12 was 10.5 +/- 6.4 mg/l. Theophylline was withdrawn in 6 patients with initial clearances less than 5 ml/kg/h (zero in 5 cases). T48 was within therapeutic values (10-20 mg/l) in 55 p. 100 of cases (21/38). Twelve patients had T48 less than 10 mg/l due to an increase in theophylline clearance (+ 80 p. 100 on average) related to improved right ventricular function in 7 cases. In 5 patients T48 was greater than 20 mg/l (max = 27.5) due to a fall in clearance (average -47 p. 100) which could have been caused by administration of erythromycin in 1 case and by dose-dependent kinetics in 2 cases. This protocol which is simple to carry out in practice allows early adjustment of dosage to give effective serum theophylline concentrations in over 50 p. 100 of cases. No serious cases of overdosage were observed, even in patients with high T0 and/or low initial clearances. Under-dosage and overdosage are related to large individual variations in theophylline clearance.
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