caa a22 4500 477126235 CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970901xx s 000 0 eng 10.1023/A:1012179529090 doi (NATIONALLICENCE)springer-10.1023/A:1012179529090 Biphasic Testosterone Delivery Profile Observed with Two Different Transdermal Formulations [Elektronische Daten] [Amit Misra, Rahul Pal, Subeer Majumdar, G. Talwar, Om Singh] Purpose. Our long-term goal is to develop formulations for pulsatile testosterone (T) delivery. T has been reported earlier to show biphasic pharmacokinetics in humans by Mazer et al, as well as biphasic permeation across excised rat skin by our group. We examined two kinds of formulations to evaluate their delivery profiles and to assess whether differences in the formulation approach affect pharmacokinetics in animal 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-through cell interfaced with an HPLC pump and UV detector. Single dose pharmacokinetics were evaluated in castrated Wistar rats and bonnet monkeys immunized against gonadotropin-releasing hormone to deplete endogenous T. Results. Two maximas were observed in the T release profile from the patch and in serum concentration versus time profiles in both animal models on application of either formulation. The relative magnitudes of the two maximas and the time interval separating them were different 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. Plenum Publishing Corporation, 1997 transdermal nationallicence testosterone nationallicence androgen supplementation nationallicence male contraception nationallicence pulsatile release nationallicence Misra Amit National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut Pal Rahul National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut Majumdar Subeer National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut Talwar G. National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut Singh Om National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1264-1268 0724-8741 14:9<1264 1997 14 11095 https://doi.org/10.1023/A:1012179529090 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012179529090 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Misra Amit National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut NATIONALLICENCE 700 1- Pal Rahul National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut NATIONALLICENCE 700 1- Majumdar Subeer National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut NATIONALLICENCE 700 1- Talwar G. National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut NATIONALLICENCE 700 1- Singh Om National Institute of Immunology, Aruna Asaf Ali Marg, 110067, New Delhi, India aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1264-1268 0724-8741 14:9<1264 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer