Evaluation of slow-release theophylline pharmacokinetics by Fourier's harmonic analysis.

Theophylline absorption from two sustained-release theophylline formulations was examined over 2 consecutive days during continuous therapy in 7 asthma patients. We compared two twice daily formulations of Teotard capsules (TC) and Teolin tablets (TT). Bioavailability for each 12-h period was defined as: BIO = (AUC oral/AUC iv) x (Dose iv/Dose oral)x100. The amount of theophylline absorbed during each 2-h interval was calculated using modified Wagner-Nelson equation for multiple dose drug administration. Mean serum theophylline concentrations were analysed by Fourier's harmonic analysis (FHA) and by F test. There were not statistically significant differences between TT and TC neither for BIO nor for fractional absorption calculated for 2-h sampling intervals. On the other hand FHA of mean SCT disclose more predictable theophylline absorption from TT compared to TC. We conclude that in order to obtain complete pharmacokinetic profile of slow-release formulation FHA should also be included into the calculations.

[Pharmacokinetics of Teolin 300 tablets and Teotard 350 capsules in asthma patients]. / Farmakokinetika tableta Teolin 300 i kapsula Teotard 350 u astmaticara.

Pharmacokinetics of tablets Teolin 300 (TT) and capsules Teotard 350 (TC) was studied in 7 asthma patients. Serum theophylline concentrations (SCT) were measured in 2-h intervals over 2 consecutive days for each theophylline formulation. A randomized, crossover design was used. In 12-h one dose of TT was absorbed 89.76 +/- 32.76% (means +/- SD) and TC 83.76 +/- 49.48%; between them there were statistically no differences. Amplitudes of SCT (AMP) were in the range 0.31 to 2.7 and mean 24-h SCT in the range 19.8 to 119.3 mumol/L. AMP were reproducible only to TT (r = 0.97, p less than 0.001). Fourier's harmonic analysis applied to mean SCT disclosed statistically significant 12-h oscillations only for TT (p less than 0.05). Continuous therapy with slow-release theophylline should always be monitored with measurements of SCT which should be interpreted by pharmacokinetics data of applied sustained theophylline formulation.