Aug. 30, 2012  13  US 2012/0220962 Al  ing hormone, y-melanocyte-stimulating hormone, melatonin,  motilin, oxytocin (pitocin), pancreatic polypeptide, parathy› roid hormone, placental lactogen, prolactin, prolactin-release  inhibiting factor, prolactin-releasing factor, secretin, soma› totropin, somatostatin, growth hormone-release inhibiting  factor, thyrotropin (thyroid-stimulating hormone, thyrotro› pin-releasing factor, thyroxine, triiodothyronine, vasoactive  intestinal peptide, vasopressin (antidiuretic hormone) and  combinations thereof.  [0122]  Particularly preferred analogues of LHRH include  buserelin, deslorelin, fertirelin, goserelin, histrelin, leupro› lide (leuprorelin), lutrelin, nafarelin, tryptorelin and combi› nations thereof.  [0123]  Other examples of hormones and hormone-related  drugs include anastrozle, betamethasone, bicalutamide, des› mopres sin, desogestrel, dexamethasone, dienestrol, dro› spirenone, estradiol, estropipate, ethinyl estradiol, ethynodiol  diaceate, exemestane, fludrocortisone ( e.g., fudrocortisone  acetate), goserelin, hydrocortisone, letrozole, leuprolide  ( e.g., leuprolide acetate), liothyronine ( e.g., liothyronine  sodium), medroxyprogesterone (e.g., medroxyprogesterone  acetate), methimazole, methylprednisolone (e.g., methyl› prednisolone acetate), methyl testosterone, norethindrone  (e.g., norethindrone acetate), norgestimate, norgestrel, oct› reotide acetate, oxandrolone, oxymetholone, prednisolone,  prednisone, progesterone, tamoxifen (e.g., tamoxifen cit› rate), testosterone, and toremifene ( e.g., toremifene citrate).  [0124]  In addition, the peptidyl drug may be a kinin. Par› ticularly preferred kinins include bradykinin, potentiator B,  bradykinin potentiator C, kallidin and combinations thereof.  [0125]  Still other peptidyl drugs that provide a desired  pharmacological activity can be incorporated into the deliv› ery systems of the invention. Examples include abarelix,  adenosine deaminase, anakinra, ancestim, alteplase, algluc› erase, asparaginase, bivalirudin, bleomycin, bombesin, des› mopres sin acetate, des-Q 14-ghrelin, domase-a, enterostatin,  erythropoietin,  exendin-4,  fibroblast  growth  factor-2,  filgrastim,  ~-glucocerebrosidase,  gonadorelin,  hyalu› ronidase, insulinotropin, lepirudin, magainin I, magainin II,  nerve growth factor, pentigetide, thrombopoietin, thymosin  a-1, thymidin kinase, tissue plasminogen activator, tryp› tophan hydroxylase, urokinase, urotensin II and combina› tions thereof.  [0126]  Particularly preferred systemically active agents  that can be administered transdermally in conjunction with  the present invention include oxytocin, insulin and LHRH  analogues, such as leuprolide.  [0127]  The methods and compositions of the invention are  expected to provide an enhanced flux of peptidyl drugs in the  range of at least about 6- to 9-fold, preferably at least about  27- to 34-fold, as compared to the flux observed in the  absence of the basic enhancers described herein.  [0128]  F. Locally Administered Active Agents  [0129]  Preferred agents for local, topical administration are  within the broad classes of compounds known to be topically  administrable, including, but not limited to, topical antibiot› ics (e.g., magainin I and magainin II), anti-acne agent, anti› fungal agents, anti-psoriatic agents, antipruritic agents, anti› histamines, antineoplastic agents ( e.g., asparaginase and  bleomycin), local anesthetics, anti-inflammatory agents and  the like.  [0130]  Suitable topical antibiotic agents include, but are not  limited to, antibiotics of the lincomycin family (referring to a  class of antibiotic agents originally recovered from  strepto- myces lincolnensis);  antibiotics of the tetracycline family (re› ferring to a class of antibiotic agents originally recovered  from  streptomyces aureofaciens);  sulfur-based antibiotics,  i.e., sulfonamides; mupirocin; and antibiotics such as magai› nin I and magainin II. Exemplary antibiotics of the lincomy› cin family include lincomycin itself (6,8-dideoxy-6-[[(1-me› thyl-4-propyl-2-pyrrolidinyl)-carbonyl]amino ]-1-thio-L› threo-a-D-galacto-octopyranoside ),  clindamycin,  the  7-deoxy, 7-chloro derivative of lincomycin (i.e., 7-chloro-6,  7,8-trideoxy-6-[[ (1-methyl-4-propyl-2-pyrrolidinyl) carbo› nyl]-amino ]-1-thio-L-threo-a-D-galacto-octopyranoside ),  related compounds as described, for example, in U.S. Pat.  Nos. 3,475,407, 3,509,127, 3,544,551 and 3,513,155, and  pharmacologically acceptable salts and esters thereof. Exem› plary antibiotics of the tetracycline family include tetracy› cline itself ( 4-( dimethylamino )-1,4,4a,5,5a,6, 11, 12a-oc› tahydro-3,6, 12, 12a-pentahydroxy-6-methyl-1, 1 ’-dioxo-2- naphthacene-carboxamide ),  chlortetracycline,  oxytetracycline, tetracycline, demeclocycline, rolitetracy› cline, methacycline and doxycycline and their pharmaceuti› cally acceptable salts and esters, particularly acid addition  salts such as the hydrochloride salt. Exemplary sulfur-based  antibiotics include, but are not limited to, the sulfonamides  sulfacetamide, sulfabenzamide, sulfadiazine, sulfadoxine,  sulfamerazine, sulfamethazine, sulfamethizole, sulfamethox› azole, and pharmacologically acceptable salts and esters  thereof, e.g., sulfacetamide sodium.  [0131]  Topical anti-acne agents include adapalene, azelaic  acid, benzoyl peroxide, clindamycin and clindamycin phos› phate, doxycycline, erythromycin, keratolytics such as sali› cylic acid and retinoic acid (Retin-A"), norgestimate, organic  peroxides, retinoids such as isotretinoin and tretinoin, sulfac› etamide sodium, and tazarotene. Preferred anti-acne agents  include adapalene, azelaic acid, benzoyl peroxide, clindamy› cin (e.g., clindamycin phosphate), doxycycline (e.g., doxy› cycline monohydrate ), erythromycin, isotretinoin, norgesti› mate, sulfacetamide sodium, tazarotene, and tretinoin.  [0132]  Exemplary  topical  antifungal  agents  include  amphotericin B, benzoic acid, butenafine and butenafine HCl,  butoconazole and butoconazole nitrate,  caprylic acid,  chloroxylenol, ciclopirox, clotrimazole,  econazole and  econazole nitrate, fluconazole, itraconazole, ketoconazole,  miconazole and miconazole nitrate, naftifine and naftifine  HCl, nystatin, oxiconazole and oxiconazole nitrate, salicylic  acid, selenium and selenium sulfide, sulconazole and sul› conazole nitrate, terbinafine and terbinafine HCl, tercona› zole, tioconazole, and undecylenic acid.  [0133]  Topical  antipsoriatic  agents  include acitretin,  alclometasone dipropionate, anthralin, azathioprine, calcipo› triene, calcitriol, colchicine, cyclosporine, methoxsalen, ret› inoids, and vitamin A.  [0134]  Exemplary local anesthetics include alcohols such  as phenol; benzyl benzoate; calamine; chloroxylenol; dyclo› nine; ketamine; menthol; pramoxine; resorcinol; troclosan;  and procaine drugs such as benzocaine, bupivacaine, chloro› procaine, cinchocaine, cocaine, dexivacaine, diamocaine,  dibucaine,  etidocaine,  hexylcaine,  levobupivacaine,  lidocaine, mepivacaine, oxethazaine, prilocalne, procaine,  proparacaine,  propoxycaine,  pyrrocaine,  risocaine,  rodocaine, ropivacaine, and tetracaine; and combinations  thereof. Derivatives of these compounds, such as pharmaceu› tically acceptable salts and esters are also of particular inter› est, for example, bupivacaine HCl, chloroprocaine HCl,  diamocaine cyclamate, dibucaine HCl, dyclonine HCl, eti-