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Henry Ford Hospital Medical Journal

Volume 18 | Number 3 Article 4

9-1970 Percutaneous Absorption of -17-Benzoate George R. Mikhail

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Recommended Citation Mikhail, George R. (1970) "Percutaneous Absorption of Betamethasone-17-Benzoate," Henry Ford Hospital Medical Journal : Vol. 18 : No. 3 , 179-186. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol18/iss3/4

This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Henry Ford Hosp. Med. Journal Vol. 18, No. 3, 1970

Percutaneous Absorption of Betamethasone-17-Benzoate

George R. Mikhail, M.D.*

Percutaneous absorption of betamethasone-17-benzoate, a new topical cortico­ , was sufficient enough to result in adrenocortical suppression in patients with psoriasis or atopic dermatitis when 0.025% of the steroid cream was applied under occlusion to 30% or more of the body surface, using 9 gm or more of the preparation. The adrenal function returned to normal within a short time after the cream was discontinued.

Since 1952^ topical lar. The enhanced therapeutic effect therapy has held the most prominent with such dressing is due to increased positions among medications used for absorption of the steroid through the the treatment of various skin diseases, skin. Using vasoconstriction as an in­ with litde fear of the sequelae that re­ dex of absorption, occlusion of the skin sult from systemic administration of surface with a plastic film was found . The possibility that to result in a one-hundred-fold differ­ topically applied could ence in absorption over simple topical be percutaneously absorbed was con­ application. There is also ample evi­ sidered soon after it came into use.^-^ dence that large amounts of corticos­ With the introduction of the fluorinated teroid creams will produce systemic derivatives of , many new effects when applied under an occlu­ compounds have been synthesized. sive dressing."'^^ The systemic effects They are characterized by greater pen­ depend upon the concentration and etrability than hydrocortisone which amount of the steroid preparation ap­ renders them more effective in treating plied, and on the size of the area dermatologic disorders.'"' '* This also treated.i»'2o accounts for the systemic effects they In the present study, the percutan­ may produce.^- eous absorption of a new steroid, beta­ In 1961 the therapeutic effectiveness methasone-17-benzoate (Fig 1), in a of corticosteroids was found to be cream base was evaluated. markedly increased when the treated skin was covered with an occlusive Methods plastic dressing.11'12 Since that time this Nine adult patients with atopic der­ therapeutic modality has become popu- matitis or psoriasis were studied for evidence of adrenocortical suppression * Department of Dermatology after application of 0.025% betametha-

179 Mikhail CHgOH

Figure 1 Chemical structure of betamethasone-17-benzoate. sone-17-benzoate in a cream base un­ determining the 8:00 AM plasma Cor­ der polyethylene film dressing to 10%, tisol levels (Table II) and the 24-hour 30%, 60% and 90% of the body urinary excretion of the 17-hydroxy­ surface (Table I). corticosteroids (17-OHCS) (Table III). The adrenocortical function was The 24-hour urinary creatinine output evaluated during two control days and served as control for the urine collec­ then daily during seven treatment days tions. Estimation of the endogenous and five to ten post-treatment days by adrenocorticotrophic hormone prodoc- Table 1 — Clinical Data

Patient No. Sex Age Disease Per cent Body Surface Treated

1 M 30 Psoriasis 10 2 M 35 Dermatitis 10 3 M 43 Psoriasis 10 4 N\ 47 Psoriasis 30 5 M 28 Dermatitis 30 6 M 23 Psoriasis 60 7 F 31 Dermatitis 60 8 M 44 Psoriasis 90 9 M 29 Dermatitis 90 180 Table II Plasma Levels (ug/100 ml) In Patients Treated c With 0.025% Betamethasone Benzoate cream CQ Patient Per cent Initial Treatment Days Post-Treatment Days No. Body Levels Treated 2 3 4 5 6 7 1 2 3 4 5 6 7 8 9 10 1 10 11.2 01 10.6 9.3 9.6 11.8 10.0 7.8 10.1 9.9 12.5 11.2 E 9.8 re 14.0 03 2 10 10.8 8.9 15.0 10.2 10.2 8.8 14.7 14.5 13.3 11.8 ca 3 10 9.0 8.6 9.9 10.4 6.9 8.8 9.3 8.0 9.3 8.0 12.2 11.5 9.6 4 30 11.5 9.0 6.6 9.3 11.9 14.6 . 12.3 13.7 13.4 12.5 8.3 9.6 8.5 o 5 30 7.3 1.7 1.8 2.3 0.0 0.0 4.1 7.6 6.0 9.3 9.0 8.3 .n 8.4 < 6 60 7.8 0.1 4.5 4.4 6.0 6.8 6.3 2.7 2.2 4.1 1.6 O 7 60 14.4 O) 7.3 13.2 10.0 9.6 11.0 7.5 10.9 15.8 20.1 15.1 13.1 c 16.0 re 4-* 8 90 10.0 3 7.5 1.0 0,0 0.0 0.0 0.0 0.0 0.0 6.0 7.0 5.2 6.6 10.0 U 14.4 03 a. 9 90 12.8 0.0 0.0 0.0 0.0 0.0 1.1 6.1 8.3 11.8 0.0 Table 111 — Urinary 17-hydroxycortlcoids In Patients Treated with 0.025% Betamethasone Benzoate cream

Patient Per cent Initial Treatment Days Post-Treatment Days No. Body Levels Treated 2 3 4 5 6 7 1 2 3 4 5 6 7 8 9 10

1 8.3 6.7 9.4 4.2 8.9 8.3 5.0 7.1 3.7 8.8 10.3 12.2 2 15.4 14.2 13.7 14.0 2.9 11.8 3 8.5 12.2 7.8 10.6 7,8 7.7 5. l* 4.9' 4.0' 3.8' 5.0 CO 11.3 1^ 4 30 10.3 9.2 10.4 7.0 7.3 7.1 7.2 5.2 6.7 7.5 8.1 10.1 5 30 10.1 7.8 5.2 4.8 2.3 3.5 1.7 3.2 3.5 6.9 7.4 10.7" 8.9 5.8 6 60 5.2 7.0 4.4 4.6 3.5 9.4 5.7 4.2 5.0 6.3 7.6 6.8 7 60 5.9 5.0 3.8 3.9 3.7 4.1 4.2 5.9 5.3 4.8 3.5 9.8" 10.5 8 90 16.4 16.8 8.1 4.3 2.1 3.3 3.1 3.5 3.2 8.0 8.7 9.4 6. 7 9.3 27.9" 18.1 10.7 9 90 10.3 3.7 2.1 2.0 2.8 2.3 1.7 2.4 4.5 8.5 7.2

Inadequate urine collections After Metyrapone Percutaneous Absorption of Betamethasone-17-Benzoate tion, evaluated in two cases, by admin­ steroid therapy and those who had istering metyrapone 650 mg every four occlusive topical steroid within the hours for six doses showed low values preceding two weeks were excluded. of 17-OCHS in the post-treatment After baseline studies were com­ period (Table III). pleted, the designated amount of the The patients were hospitaliz:ed and, cream was applied evenly, massaged in addition to the adrenal function tests, into the skin and covered with an the following tests were performed in occlusive plastic dressing. The dressing each case before beginning the treat­ was left in place for 12 hours (6:00 ment and two days after the conclusion PM to 6:00 AM). When the dressing of the treatment: CBC, BUN, SGOT, was removed, the patient took a bath urinalysis, serum alkaline phosphatase without scrubbing, and the therapeutic and two-hour post-Glucola® blood response was noted. sugar determination. Only patients in Three to four gm of cream were whom normal values were obtained needed to cover 10% of the body sur­ entered the study. face, while 9 to 13 gm, 18 to 24 gm All types of medication were sus­ and 27 to 36 gm were necessary to pended with the exception of the cover 30%, 60% and 90% of the emergency use of diphenhydramine surface, respectively. hydrochloride for sedation. Petrolatum was applied to the untreated areas Results when needed. Patients on systemic There was no appreciable reduction I4-.

12- 30% BODY 10- CASE 4 PLASMA 8- CORTISOL jjg/IOOml.

I I I—r—I—r-i—r-i—r 23 45671234567 ^TREATMENT—^^POST-TREATMENT^I DAYS Figure 2 Plasma Cortisol levels with 30% body surface treatment.

183 Mikhail

PLASMA CORTISOL 12 >jg/IOOml. 10-

1—\—I—I—I—r T—I—I—r I 2 3 4 5 6 7 2 3 4 5 6 ^ TREATMENT POST- _f TREATMENT DAYS Figure 3 Plasma Cortisol levels with 60% body surface treatment. in adrenal secretion when 10% of the all cases. With 60% and 90% coverage body was treated. When 30% or more distant untreated lesions improved at surface area was treated, the plasma the same rate as those treated, indicat­ Cortisol and 17-OHCS became mark­ ing absorption into the circulation of edly decreased, most strikingly with substantial amounts of the steroid. No 90% occlusion (Tables II, III, Fig 2-4). adverse effects were noted. In the latter case, the plasma Cortisol decreased to zero after the first appli­ Acknowledgement cation of the steroid. Normal levels were reached within three or four days This study was undertaken through after cessation of treatment except in research grant No. 501 from Henry Case No. 8 (at 10 days). Ford Hospital and financial support Favorable therapeutic response oc­ from Warner-Lambert Research In­ curred promptly and was excellent in stitute.

184 Percutaneous Absorption of Betamethasone-17-Benzoate

114- o 5 12 \ =^10 _l O Q. CO o cr o o

cn

"""1—I—I—\—r T—I—I—I—I—I—I—I—r 2 3 4 5 6 234 56789 10 >4_ TREATMENT- -POST-TREATMENT-* DAYS

Figure 4

Plasma Cortisol levels with 90% body surface treatment.

REFERENCES

1. Sulzberger, M. B., and Witten, V. H.: The effect of topically applied compound F in selected dermatoses. J Invest Derm 19:101-2, Aug 1952. 2. Sulzberger, M. B.; Witten, V. H., and Smith, C. C: Hydrocortisone (Compound F) acetate ointment in dermatological therapy. JAMA 151:468-72, 7 Feb 1953. 3. Gemzell, C. A.; Hard, S., and Nilzen, A.: The effect of hydrocortisone, applied locally to the skin, on the eosinophil count and the plasma level of 17-hydroxycortisteroids. Acta Dermato Vener 35:327-33, 1955. 4. Malkinson, F. D.: Studies on the percutaneous absorption of Cu labeled by use of gas-flow cell. / Invest Derm 31:19-28, Jul 1958. 5. Fried, J., and Sabo, E. F.: 9a-fluoro derivatives of cortisone and hydrocortisone. J Amer Chem Soc 76:1455-6, 5 Mar 1954. 6. Wright, E. T., et al: Evaluation of 9-a-fluorohydrocortisone acetate in the treatment of various inflammatory dermatoses. Arch Derm 72:69-71, Jul 1955. 7. Witten, V. H., et al: A therapeutic assay of topically applied 9-a-fluorohydrocortisone acetate in selected dermatoses. J Invest Derm 24:1-4, Jan 1955. 8. Robinson, R. C. V.: Use of fluorocortisone acetate in dermatoses. JAMA 157:1300-2, 9 Apr 1955. 9. Fitzpatrick, T. B.; Griswold, H. C, and Hicks, J. H.: Sodium retention and edema from percutaneous absorption of acetate. JAMA 158:1149-52, 30 Jul 1955.

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10. Livingood, C. S.. et al: Studies on the percutaneous absorption of fludrocortisone. Arch Derm 72:313-27, Oct 1955. 11. Sulzberger, M. B., and Witten, V. H.: Thin pliable plastic films in topical dermatologic therapy. Arch Derm 84:1027-8, Dec 1961. 12. Scholtz, J. R.: Topical therapy of psoriasis with acetonide. Arch Derm 84:1029-30, Dec 1961. 13. McKenzie, A. W., and Stoughton, R. B.: Method for comparing percutaneous absorption of steroids. Arch Derm 86:608-10, Nov 1962. 14. Scoggins, R. B.: Decrease of urinary corticosteroids following application of under an occlusive dressing. J Invest Derm 39:473-4, Dec 1962. 15. Gill, K. A., and Baxter, D. L.: Plasma Cortisol suppression by steroid creams. Arch Derm 89:734-40, May 1964. 16. Kirketerp, M.: Systemic effects of local treatment with fluocinolone acetonide applied under plastic film. Acta Derm 44:54-62, 1964. 17. March, C, and Kerbel, G: Adrenal function after application of topical steroids under occlusive plastic film. JAMA 187:676-8, 29 Feb 1964. 18. Taylor, K. S.; Malkinson, F. D., and Gak, C: Pituitary-adrenal function following topical acetonide and occlusion. Arch Derm 92:174-7, Aug 1965. 19. Fry, L., and Wight, D. G. D.: Plasma Cortisol levels after topical use of fluocinolone acetonide. Brit J Derm 77:582-5, Nov 1965. 20. James, V. H. T.; Munro, D. D., and Feiwel, M.: Pituitary-adrenal function after occlusive topical therapy with betamethasone-17-valerate. Lancet 2:1059-61, 18 Nov 1967.

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