Components of variability in serum theophylline concentrations during maintenance therapy with a sustained release formulation

H. Halkin*, A. Mazar, S. Almog, Y. Schnaps

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)225-228
Number of pages4
JournalEuropean Journal of Clinical Pharmacology
Volume23
Issue number3
DOIs
StatePublished - May 1982

Keywords

  • accumulation
  • asthma
  • dosage prediction
  • serum concentrations
  • sustained-release
  • theophylline
  • variability

Fingerprint

Dive into the research topics of 'Components of variability in serum theophylline concentrations during maintenance therapy with a sustained release formulation'. Together they form a unique fingerprint.

Cite this