BIPHASIC TESTOSTERONE DELIVERY PROFILE OBSERVED WITH 2 DIFFERENT TRANSDERMAL FORMULATIONS

Purpose. Our long-term goat is to develop formulations for pulsatile t estosterone (T) delivery. T has been reported earlier to show biphasic pharmacokinetics in humans by Mazer et al, as well as biphasic permea tion across excised rat skin by our group. We examined two kinds of fo rmulations to evaluate their delivery profiles and to assess whether d ifferences in the formulation approach affect pharmacokinetics in anim al models. Methods, One formulation consisted of T and a polymer blend dissolved in isopropanol; administered by dispensing the solution on the skin to cast a film in situ. The other was an adhesive-dispersion patch. In vitro release from the patch was evaluated using a flow-thro ugh cell interfaced with an HPLC pump and UV detector. Single dose pha rmacokinetics were evaluated in castrated Wistar rats and bonnet monke ys immunized against gonadotropin-releasing hormone to deplete endogen ous T. Results. Two maximas were observed in the T release profile fro m the patch and in serum concentration versus time profiles in both an imal models on application of either formulation. The relative magnitu des of the two maximas and the time interval separating them were diff erent in the case of each formulation, Conclusions, Both formulations result in biphasic pharmacokinetics of T in the animal models studied. Discrete maximas presumably correlate with ''burst'' and ''sustained' ' phases of drug release.