Population pharmacokinetic analysis of theophylline: relationship between serum concentrations and clinical effects in therapeutic drug monitoring

Tanikawa, K.; Matsumoto, Y.; Matsuzaki, T.; Matsumoto, M.; Fukuoka, M.; Noguchi, S.; Goshima, T.

Yakugaku Zasshi Journal of the Pharmaceutical Society of Japan 119(11): 861-867

1999


ISSN/ISBN: 0031-6903
PMID: 10590713
DOI: 10.1248/yakushi1947.119.11_861
Accession: 011169118

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Abstract
Therapeutic drug monitoring (TDM) of theophylline is essential duties at hospital pharmacy in Japan. The relationship between serum concentrations and clinical effects of theophylline has been investigated. The pharmacokinetics of theophylline was determined from the concentration of theophylline in the serum which were calculated on the basis of TDM for patients administered theophylline. The one-compartment model as a pharmacokinetic model was assumed. The relationship between clinical effects of theophylline and the predicted concentrations calculated using population parameters was evaluated. The obtained parameters are ka(h-1)=0.223, ke(h-1)=0.047(1-0.0025cntdotage(y) (p.o.) and 0.076(1-0.0025cntdotage(y)) (d.i.v.), Vd(1/kg)=0.733 (p.o.) and 0.830 (d.i.v.). The bioavailability is 0.732, and theophylline/aminophylline is 0.846. The model including no serum creatinine as a variational factor was considered to be best. The following three groups were used as a clinical evaluation; effective as theophylline therapy was 43%, no change of the clinical status after administration of theophylline was 42%, and aggravation after administration of theophylline was 15%. There is no relationship between the predicted concentration using parameters of the final model and these three groups. These results suggest that TDM of theophylline should be assessed in terms of clinical effects and also suggests that in should be kept monitoring from the viewpoint of the prevention of toxic effects in the theophylline therapy.