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Chronopharmacokinetics of theophylline after sustained release and intravenous administration to adults.

Abstract：

: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 different p greater than 0.05). The maximum plasma concentrations were almost identical after administration in the morning and in the evening (12.6 +/- 3.3 mg X l-1 and 13.1 +/- 1.4 mg X l-1 respectively). There was also no significant difference (p greater than 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: c1 12 accounted for 6.0 +/- 2.0 mg X l-1 after intake at 10 a.m. and for 7.9 +/- 2.1 mg X l-1 after ingestion at 10 p.m. (p less than 0.01). A similar observation was done after intravenous administration of the drug: c12 was 6.6 +/- 1.6 mg X l-1 after starting the infusion in the morning and 8.0 +/- 1.8 mg X l-1 after infusing the drug in the evening (p less than 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 X l-1 (which coincides approximately with the therapeutic range of the drug).(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Jonkman JH,van der Boon WJ,Balant LP,Schoenmaker R,Holtkamp A

doi

10.1007/BF00630288

subject

Has Abstract

pub_date

1984-01-01 00:00:00

pages

215-22

issue

eissn

0031-6970

issn

1432-1041

journal_volume

pub_type

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Chronopharmacokinetics of theophylline after sustained release and intravenous administration to adults.