Allergy.  1994 Dec;14(4):638-646.

Comparison of slow-releasing form-ulations of theophylline; pharmacokinetic study and in vitro release assay

• Yoon HJ
• Jee YK
• Choi DC
• Kim YY
• Cho SH
• Min KU
• Kim YK
• Kim HS
• Song SH
• Shin HT

Abstract

Theophylline has a narrow therapeutic range and the serum level is determined by rate of theophylline elimination in individual patient, releasing and absorption characteristics of the formulations and the dosing interval. We already reported the theophylline clearance in Korean adult asthmatics. To evaluate the releasing and absorption characteristics of the several kinds of slow releasing formulations(Somophylline(r), Theoclear(r), Asthcontin(r), Theolan(r), we compared absorption rate constant(Ka), bioavailibility, fluctuation ratio of the formulations. Fourteen asthmatic patients(25~67 years old) were randomly allocated to each formulation and cross-overed. Serum theophylline levels were assessed serially between dosing intervals at steady state. And in vitro releasing assay of the formulations were performed in simulated gastric fluid(pH 1.2) and intestinal fluid (pH 7.5). And it was also performed in simulated intestinal fluid after dissolution in gastric fluid for the first hour. Theophylline levels were assessed by HPLC and the results were as follows: 1) Somophylline(r) and Asthcontin(r) showed low fluctuation ratios (<1.0) when administered both every 12 hours and 8 hours. Theoclear(r) showed relatively high fluctuation ratio(1.39+/-1.0) when administered every 12 hours, while showed very low fluctuation (0.25 +/- 0.31) when administered every 8 hours. However Theolan(r) showed very high fluctuation ratio(3.10+/-1.31)when administered every 24 hours. 2) Except Theolan(r), nothing showed significant difference with others in terms of intervals for peak serum level(Tmax) after dosing and abosorption rate constant(Ka). 3) Asthcontin(r) showed relatively constant release in simulated gastric and intestinal fluid, suggesting that it was not dependent on pH. Somophylline(r) showed moderate increase of release when it was transferred into simulated intestinal fluid after release in gastric fluid for an hour than in intestinal fluid form the beginning. And Theoclear(r) showed dramatic release of the formulation if it was transfeted into simulated intestinal fluid after release in gastric fluid for an hour(form 8.7% to 82.8% release during 30 minutes). Above results suggest that there are significant differences in releasing characteristics among several kinds of slow-releasing formulations, even if they showed similar fluctuations of serum theophylline levels. For the effective and safe use of oral theophyllines, we have to consider not only release and absorption characteristics but also elimination rate of theophylline in individual patient.

MeSH Terms

Absorption
Adult
Chromatography, High Pressure Liquid
Humans
Hydrogen-Ion Concentration
Theophylline*
Theophylline