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Pharmacokinetics of transdermally delivered clonidine
Author(s) -
MacGregor Thomas R,
Matzek Kandace M,
Keirns James J,
Wayjen Rudolf G A,
Ende Abraham,
Tol Rudolf G L
Publication year - 1985
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1985.171
Subject(s) - clonidine , transdermal , pharmacokinetics , steady state (chemistry) , anesthesia , medicine , plasma concentration , chemistry , pharmacology
We detail a series of pharmacokinetic investigations to determine the dose linearity, the effect of site of application, the duration of steady‐state plasma concentrations, and the effect of chronic application when clonidine is administered transdermally. Dose linearity was assessed in six subjects with normotension after application of increasing sizes of transdermal clonidine systems (3.5, 7.0, and 10.5 cm 2 size) to the upper outer arm. Of the six subjects studied, five had linear relationships between clonidine plasma concentrations at steady state and system size of >0.975; in the sixth subject the correlation was >0.90. The mean steady‐state plasma concentrations with 3.5, 7.0, and 10.5 cm 2 systems were 0.39, 0.84, and i.12 ng/ml, respectively. The influence of site and duration of application on the absorption of transdermal clonidine was studied in eight subjects with normotension by use of the 3.5 cm 2 system. The mean steady‐state plasma concentration over the time interval from 3 to 7 days after application to the arm or to the chest did not significantly differ. When a system was left on the chest or arm for a total of 11 days (4 days beyond the recommended time to change systems), the plasma concentrations of seven of eight subjects with application to the arm and of six of eight subjects with application to the chest remained constant through day 11. The influence of consecutive applications of 3.5 cm 2 transdermal clonidine systems on steady‐state plasma clonidine concentrations was also studied in eight subjects with normotension over an 11‐day period. Steady‐state plasma concentrations were achieved in all eight subjects within 3 days after application of the initial transdermal clonidine system. On days 4 and 7 the previous transdermal system was removed and a new system was applied to the alternate arm. The mean steady‐state plasma concentration (3 to 11 days) for the eight subjects was 0.32 ng/ml. There was no apparent difference between the mean plasma concentration at the time the clonidine system was removed and 24 hours after application of a new system. Clinical Pharmacology and Therapeutics (1985) 38, 278–284; doi: 10.1038/clpt.1985.171