Dose linearity of clonidine after transdermal application.
A prerequisite for optimal antihypertensive treatment is the possibility of individualized dosing. Therefore, three different dosages of the clonidine containing transdermal systems have been developed. The aim of this analysis was to clarify whether a linear enlargement of system size and consequently, a linear increase of the dose coming into contact with the skin will result in a linear increase of bioavailable drug. Data sets were obtained from a study performed in healthy volunteers, who wore these different TTS systems for 7 days each. Every patch was analysed after removal for residual content of clonidine. Plasma levels were measured. The areas under these plasma level curves were calculated by the trapezoidal rule. Apart from the dose of clonidine in the patch, the actual released amount of drug from the patch as well as the area under the plasma level curve were the parameters selected for the data analyses. Plasma levels of clonidine are known to vary within individuals. However, we have shown that within the range 2.5-7.5 mg of clonidine, the area under the plasma level curve as well as the released amounts of drug increase linearly with the dose administered. The regression analysis of released amounts versus the area under the plasma level curve further supports linearity of dosage.
Wallenstein
G
G
Department of Research and Development, Boehringer Ingelheim KG, Ingelheim, Germany.
Gladigau
V
V
D000279:Administration, Cutaneous; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D003000:Clonidine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D012044:Regression Analysis
D000959:Antihypertensive Agents; D003000:Clonidine