Components of variability in serum theophylline concentrations during maintenance therapy with a sustained release formulation
Tóm tắt
Fifteen adult chronic asthmatic patients were studied on 6 consecutive days of the second week of treatment with a new sustained release theophylline formulation, and 8 were again studied after three months on the same dosing regimen (375 mg b.i.d.). Serum theophylline concentrations were maintained in the therapeutic range (peak −19.7±5.0 µg/ml; through −13.0±3.2 µg/ml) throughout the 12 hour dosing interval, and were greater than 75% of the peak concentration over 8.6±2.9 h. A degree of drug accumulation was evident in that the 1-h and 5-h levels rose from 12.2±4.1 and 14.5±4.8 µg/ml during the second week to 16.9±4.6 and 18.4±4.5 µg/ml, respectively, at three months. Between-patient differences accounted for 61%–71% of the total variation in steady state theophylline concentrations. After accounting for differences due to sampling time and assay error, unexplained random, within-individual variability amounted to 11%–18% of the total. Quantitative estimation of these components of variability may be incorporated into dosage forecasting methods based on single determinations of serum concentration.
Tài liệu tham khảo
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