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Veterinary research communications2006; 31(2); 227-233; doi: 10.1007/s11259-006-3446-6

Vehicle effects on the in vitro penetration of testosterone through equine skin.

Abstract: The effects of three vehicles, phosphate-buffered saline (PBS), ethanol (50% in PBS w/w) and propylene glycol (50% in PBS w/w) on in vitro transdermal penetration of testosterone was investigated in the horse. Skin was harvested from the thorax of five Thoroughbred horses after euthanasia and stored at -20 degrees C until required. The skin was then defrosted and placed into Franz-type diffusion cells, which were maintained at approximately 32 degrees C by a water bath. Saturated solutions of testosterone, containing trace amounts of radiolabelled [14C]testosterone, in each vehicle were applied to the outer (stratum corneum) surface of each skin sample and aliquots of receptor fluid were collected at 0, 2, 4, 8, 16, 20, 22 and 24 h and analysed for testosterone by scintillation counting. The maximum flux (Jmax) of testosterone was significantly higher for all sites when testosterone was dissolved in a vehicle containing 50% ethanol or 50% propylene glycol, compared to PBS. In contrast, higher residues of testosterone were found remaining within the skin when PBS was used as a vehicle. This study shows that variability in clinical response to testosterone could be expected with formulation design.
Publication Date: 2006-12-26 PubMed ID: 17191091DOI: 10.1007/s11259-006-3446-6Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article investigates how three different substances (phosphate-buffered saline, ethanol, and propylene glycol) affect the penetration of testosterone into horse skin. The study found that ethanol and propylene glycol significantly increased testosterone penetration, while phosphate-buffered saline increased the amount of testosterone remaining in the skin.

Research Objective

  • The main goal of the study was to understand the effect of three different substances, namely phosphate-buffered saline (PBS), ethanol (50% in PBS w/w) and propylene glycol (50% in PBS w/w), on the in vitro (in a controlled lab environment) transdermal penetration of testosterone in horse skin.

Methodology

  • The researchers used skin harvested from the thorax of five Thoroughbred horses after euthanasia as subjects for the experiment.
  • The collected skin was stored at -20 degrees Celsius until required for the experiment.
  • The skin was then defrosted and placed into Franz-type diffusion cells that were maintained at approximately 32 degrees Celsius by a water bath.
  • Saturated solutions of testosterone, containing trace amounts of radiolabelled [14C]testosterone, in each vehicle were applied to the outer surface of each skin sample.
  • Aliquots of receptor fluid were collected at specific time intervals and analysed for the presence of testosterone by scintillation counting.

Results

  • The experiment found that the maximum flux (Jmax) of testosterone was significantly higher when it was dissolved in a vehicle containing 50% ethanol or 50% propylene glycol, as compared to PBS.
  • In contrast, when PBS was used as a vehicle, higher residues of testosterone were found within the horse skin.

Conclusion

  • The research concludes that the choice of substance in which testosterone is dissolved (the vehicle) has a significant impact on the penetration of the hormone into the skin.
  • This result suggests that different testosterone formulations could lead to variable clinical responses, which is useful information for medical professionals involved in designing hormone treatments for horses or possibly other mammals.

Cite This Article

APA
Mills PC. (2006). Vehicle effects on the in vitro penetration of testosterone through equine skin. Vet Res Commun, 31(2), 227-233. https://doi.org/10.1007/s11259-006-3446-6

Publication

ISSN: 0165-7380
NlmUniqueID: 8100520
Country: Switzerland
Language: English
Volume: 31
Issue: 2
Pages: 227-233

Researcher Affiliations

Mills, P C
  • School of Veterinary Science, University of Queensland, Brisbane, Queensland, Australia. p.mills@uq.edu.au

MeSH Terms

  • Administration, Cutaneous
  • Animals
  • Ethanol / pharmacology
  • Horses / metabolism
  • In Vitro Techniques
  • Pharmaceutical Vehicles / pharmacology
  • Propylene Glycol / pharmacology
  • Skin Absorption
  • Sodium Chloride / pharmacology
  • Testosterone / administration & dosage
  • Testosterone / pharmacokinetics

References

This article includes 23 references
  1. Riviere JE, Papich MG. Potential and problems of developing transdermal patches for veterinary applications.. Adv Drug Deliv Rev 2001 Sep 1;50(3):175-203.
    pubmed: 11500227doi: 10.1016/s0169-409x(01)00157-0google scholar: lookup
  2. Hueber F, Schaefer H, Wepierre J. Role of transepidermal and transfollicular routes in percutaneous absorption of steroids: in vitro studies on human skin.. Skin Pharmacol 1994;7(5):237-44.
    pubmed: 7519865doi: 10.1159/000211300google scholar: lookup
  3. Finnin BC, Morgan TM. Transdermal penetration enhancers: applications, limitations, and potential.. J Pharm Sci 1999 Oct;88(10):955-8.
    pubmed: 10514338doi: 10.1021/js990154ggoogle scholar: lookup
  4. Hueber F, Wepierre J, Schaefer H. Role of transepidermal and transfollicular routes in percutaneous absorption of hydrocortisone and testosterone: in vivo study in the hairless rat.. Skin Pharmacol 1992;5(2):99-107.
    pubmed: 1637565doi: 10.1159/000211026google scholar: lookup
  5. Idson B. Vehicle effects in percutaneous absorption.. Drug Metab Rev 1983;14(2):207-22.
    pubmed: 6341025doi: 10.3109/03602538308991389google scholar: lookup
  6. Aungst BJ, Blake JA, Hussain MA. Contributions of drug solubilization, partitioning, barrier disruption, and solvent permeation to the enhancement of skin permeation of various compounds with fatty acids and amines.. Pharm Res 1990 Jul;7(7):712-8.
    pubmed: 2395798doi: 10.1023/a:1015859320604google scholar: lookup
  7. Handelsman DJ, Conway AJ, Boylan LM. Pharmacokinetics and pharmacodynamics of testosterone pellets in man.. J Clin Endocrinol Metab 1990 Jul;71(1):216-22.
    pubmed: 2115044doi: 10.1210/jcem-71-1-216google scholar: lookup
  8. Mills PC, Magnusson BM, Cross SE. Effects of vehicle and region of application on absorption of hydrocortisone through canine skin.. Am J Vet Res 2005 Jan;66(1):43-7.
    pubmed: 15691034doi: 10.2460/ajvr.2005.66.43google scholar: lookup
  9. Tur E, Maibach HI, Guy RH. Percutaneous penetration of methyl nicotinate at three anatomic sites: evidence for an appendageal contribution to transport?. Skin Pharmacol 1991;4(4):230-4.
    pubmed: 1789984doi: 10.1159/000210956google scholar: lookup
  10. Surber C, Wilhelm KP, Hori M, Maibach HI, Guy RH. Optimization of topical therapy: partitioning of drugs into stratum corneum.. Pharm Res 1990 Dec;7(12):1320-4.
    pubmed: 2095573doi: 10.1023/a:1015958526423google scholar: lookup
  11. Qiao GL, Riviere JE. Significant effects of application site and occlusion on the pharmacokinetics of cutaneous penetration and biotransformation of parathion in vivo in swine.. J Pharm Sci 1995 Apr;84(4):425-32.
    pubmed: 7629731doi: 10.1002/jps.2600840408google scholar: lookup
  12. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery.. Eur J Pharm Sci 2001 Sep;14(2):101-14.
    pubmed: 11500256doi: 10.1016/s0928-0987(01)00167-1google scholar: lookup
  13. Oriba HA, Bucks DA, Maibach HI. Percutaneous absorption of hydrocortisone and testosterone on the vulva and forearm: effect of the menopause and site.. Br J Dermatol 1996 Feb;134(2):229-33.
    pubmed: 8746334
  14. Kao J, Carver MP. Cutaneous metabolism of xenobiotics.. Drug Metab Rev 1990;22(4):363-410.
    pubmed: 2253557doi: 10.3109/03602539009041089google scholar: lookup
  15. Cantrill JA, Dewis P, Large DM, Newman M, Anderson DC. Which testosterone replacement therapy?. Clin Endocrinol (Oxf) 1984 Aug;21(2):97-107.
  16. Ostrenga J, Steinmetz C, Poulsen B. Significance of vehicle composition. I. Relationship between topical vehicle composition, skin penetrability, and clinical efficacy.. J Pharm Sci 1971 Aug;60(8):1175-9.
    pubmed: 5127090doi: 10.1002/jps.2600600812google scholar: lookup
  17. Hadgraft J. Recent developments in topical and transdermal delivery.. Eur J Drug Metab Pharmacokinet 1996 Apr-Jun;21(2):165-73.
    pubmed: 8839691doi: 10.1007/BF03190266google scholar: lookup
  18. Snow DH. Anabolic steroids.. Vet Clin North Am Equine Pract 1993 Dec;9(3):563-76.
    pubmed: 8299016doi: 10.1016/s0749-0739(17)30386-3google scholar: lookup
  19. Flynn GL, Dürrheim H, Higuchi WI. Permeation of hairless mouse skin II: membrane sectioning techniques and influence on alkanol permeabilities.. J Pharm Sci 1981 Jan;70(1):52-6.
    pubmed: 7014828doi: 10.1002/jps.2600700109google scholar: lookup
  20. Kim MK, Lee CH, Kim DD. Skin permeation of testosterone and its ester derivatives in rats.. J Pharm Pharmacol 2000 Apr;52(4):369-75.
    pubmed: 10813545doi: 10.1211/0022357001774101google scholar: lookup
  21. Monteiro-Riviere NA, Inman AO, Riviere JE, McNeill SC, Francoeur ML. Topical penetration of piroxicam is dependent on the distribution of the local cutaneous vasculature.. Pharm Res 1993 Sep;10(9):1326-31.
    pubmed: 8234171doi: 10.1023/a:1018973814456google scholar: lookup
  22. Snyder PJ. Clinical use of androgens.. Annu Rev Med 1984;35:207-17.
  23. Scheuplein RJ, Blank IH. Mechanism of percutaneous absorption. IV. Penetration of nonelectrolytes (alcohols) from aqueous solutions and from pure liquids.. J Invest Dermatol 1973 May;60(5):286-96.
    pubmed: 4758734doi: 10.1111/1523-1747.ep12723090google scholar: lookup

Citations

This article has been cited 2 times.
  1. Dahlizar S, Futaki M, Okada A, Yatomi C, Todo H, Sugibayashi K. Combined Use of N-Palmitoyl-Glycine-Histidine Gel and Several Penetration Enhancers on the Skin Permeation and Concentration of Metronidazole.. Pharmaceutics 2018 Sep 20;10(4).
    doi: 10.3390/pharmaceutics10040163pubmed: 30241371google scholar: lookup
  2. Stahl J, Kietzmann M. The effects of chemical and physical penetration enhancers on the percutaneous permeation of lidocaine through equine skin.. BMC Vet Res 2014 Jun 20;10:138.
    doi: 10.1186/1746-6148-10-138pubmed: 24950611google scholar: lookup