A theophylline dosage regimen which reduces round-the-clock variations in plasma concentrations resulting from diurnal pharmacokinetic variation |
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Authors: | M. B. Regazzi R. Rondanelli E. Vida F. Farinelli R. A. Upton |
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Affiliation: | (1) Clinical Pharmacokinetic Section and Department of Pharmacology, Scientific Institute of Admission and Treatment, San Matteo General Hospital, University of Pavia, Pavia, Italy;(2) Department of Pharmacy, University of California, San Francisco, California, USA |
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Abstract: | Summary Slower drug absorption at night can leave residual drug from an evening dose of a sustained-release product remaining to be absorbed at the time of the next morning's dose, thereby giving higher plasma concentrations of the drug during the day than the night.When a capsule product releasing theophylline over 12 h after a morning dose was given repetitively at 8 a.m. and 8 p.m. for 4 days, daytime plasma concentrations from 4 h to 8 h after the dose were about 40% greater than corresponding night-time concentrations, and the mean steady-state concentration during the night-time interval was only 81% of that during the daytime interval.Altering the regimen to one capsule at 12 noon and one at 10 p.m. eliminated all significant differences between a.m. and corresponding p.m. plasma concentrations of theophylline and between the mean steady-state concentrations for each of the interdose intervals within a day. |
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Keywords: | theophylline diurnal kinetic variation constant plasma concentration sustained release |
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