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  • 1
    ISSN: 1432-1041
    Keywords: theophylline ; sustained release tablet ; absolute bioavailability ; pharmacokinetics ; individual dosage regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic disposition of theophylline after taking a new, sustained release tablet (Theolair Retard® 250 mg, Theolair S. R.®, Riker Laboratories) has been studied in 8 hospitalized patients. Absolute bioavailability was determined from the ratios of the areas under the serum concentration-time curves after intake of the tablet and after intravenous infusion of aminophylline in the same patient. The absolute bioavailability of Theolair Retard® 250 mg was 110.9±20.8% (mean ± SD). Maximal serum concentrations were reached after 7.3±3.5 h, the large intersubject variation being due to differences in gastric emptying time. The tablets appear to release theophylline slowly in acid conditions, but more rapidly in an alkaline medium. Invasion was found to be either monophasic with a rate constant of about 0.8 h−1 (intestine), or biphasic with rate constants of 0.2 h−1 (stomach) and 0.8 h−1 (intestine). The peak levels accounted for 7.9±2.2 mg · 1−1. The profiles of the serum concentration-time curves were such that the concentrations remained above 80% of cmax for 6.5±3.3 h. The relevant pharmacokinetic parameters (half-life of elimination, total body clearance and volume of distribution) were determined and were used to calculate the individual dosage regimens required to obtain therapeutic serum concentrations. The optimal dosing interval to obtain an average steady state serum concentration of 12.5 mg · l−1 was 9.8±3.1 h.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 215-222 
    ISSN: 1432-1041
    Keywords: theophylline ; chronopharmacokinetics ; sustained release tablet ; intravenous administration ; absolute bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of time of drug administration on pharmacokinetics of theophylline was studied both after ingestion of a sustained-release tablet, containing choline theophyllinate (Zy 15061-S. R.; Teovent®; Sabidal®; ZYMA S.A.) and after intravenous infusion of aminophylline to eight healthy volunteers. Both drugs were administered in the morning (10 a.m.) and on a separate occasion in the evening (10 p.m.) after a 12 h period of fasting. After oral administration of a dose of 540 mg theophylline, the drug was steadily absorbed, both during day-time and during night-time. In some subjects absorption was slower in the evening. Maximum theophylline plasma concentrations were reached after 3.3±0.4 h (mean±SD) and 3.9±1.4 h respectively (not significantly differentp〉0.05). The maximum plasma concentrations were almost identical after administration in the morning and in the evening (12.6±3.3 mg·l−1 and 13.1±1.4 mg·l−1 respectively). There was also no significant difference (p〉0.05) between the areas under the plasma concentration-time curves after oral and intravenous administration, both at day-time and at night-time. This finding indicates complete bioavailability of the sustained release tablets on both occasions. After administration of the tablets in the morning the plasma concentration 12 h post dosing was significantly lower than after administration in the evening: c 12 1 accounted for 6.0±2.0 mg·l−1 after intake at 10 a.m. and for 7.9±2.1 mg·l−1 after ingestion at 10 p.m. (p〈0.01). A similar observation was done after intravenous administration of the drug: c12 was 6.6±1.6 mg·l−1 after starting the infusion in the morning and 8.0±1.8 mg·l−1 after infusing the drug in the evening (p〈0.01). This phenomenon could be explained by the finding of a significantly prolonged half-life of theophylline during night-time, provided that the plasma concentrations were in the range of 5 to 15 mg·l−1 (which coincides approximately with the therapeutic range of the drug). For day-time elimination the half-life of theophylline was found to be 6.2±0.9 h and for night-time elimination 8.0±2.0 h (p〈0.01), which means an increase of 29.6±20.9% during the night. The prolonged half-life of theophylline at night-time might be of therapeutic benefit in preventing bronchus obstruction in the morning.
    Type of Medium: Electronic Resource
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