title: Testosterone 17beta-N,N-dimethylglycinate hydrochloride: A prodrug with a potential for nasal delivery of testosterone.
abstract: The purpose of this study was to examine the potential of the nasal route for the systemic delivery of the poorly water-soluble drug testosterone (TS) using a water-soluble prodrug, TS 17beta-N,N-dimethylglycinate hydrochloride. The physicochemical properties of the prodrug, in vitro hydrolysis in human liver homogenate, and in vivo nasal and intravenous experiments were performed in rats. The aqueous solubility of the prodrug was more than 100 mg/mL, compared with 0.01 mg/mL for TS, and its log partition coefficient between 0.05 M, phosphate buffer (pH 6) and octanol was 2.4. The prodrug was found to generate TS in 33% human liver homogenate and was absorbed from the nasal cavity rapidly and quantitatively. The bioavailabilities of both the prodrug and TS after nasal administration of the prodrug were similar to that after equivalent intravenous doses. These studies in rats suggest that this water-soluble prodrug of TS may have therapeutic utility for the management of TS deficiency.
authors.affiliation: College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536-0082, USA. aahuss1@pop.uky.edu
authors.forename: Anwar A
authors.initials: AA
authors.lastname: Hussain
authors.forename: Ansam A
authors.initials: AA
authors.lastname: Al-Bayatti
authors.forename: Adnan
authors.initials: A
authors.lastname: Dakkuri
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Okochi
authors.forename: Munir A
authors.initials: MA
authors.lastname: Hussain
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013739:Testosterone / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics*
chemical_list: D011355:Prodrugs; C457800:testosterone 17beta-N,N-dimethylglycinate hydrochloride; D013739:Testosterone