RE: TRANSDERMAL APPLICATION OF VERAPAMIL GEL TO THE PENILE SHAFT FAILS TO INFILTRATE THE TUNICA ALBUGINEA

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To the Editor. 

We read with interest the study by Martin et al concerning the transdermal application of verapamil for Peyronie’s disease, and would like to comment on several aspects of their work. In their small study of 8 patients who did not have Peyronie’s disease verapamil was applied only twice before surgery and removed before penile prosthesis implantation surgery. It is highly unlikely that 2 applications would result in equilibration between epidermal tissue and the tunica albuginea. Importantly, clinical responses do not usually occur before 90 days of treatment, and the application is inconsistent with observed clinical responses. Application occurred over only the sides of the penile shaft and not the entire penile shaft, as done by Fitch and Easterling.¹

Furthermore, few details are provided concerning active ingredient, and no information is provided regarding whether verapamil or verapamil hydrochloride was used. Verapamil hydrochloride is preferred due to its stability. Verapamil base is unstable. The authors refer to the medication as “verapamil gel.” Drug vehicle selection and compounding technique are critical. The vehicle must be designed to traverse the stratum corneum to the extent that it reaches subdermal diseased connective tissue but at the same time minimizes systemic absorption.

The compounding procedure must be reproducible and must provide a product of consistent characteristics such as viscosity, particle size, pH and appearance. Stability of compounded verapamil is a problem, and it must be protected from light to prevent degradation, and packaged in a material that is nonreactive chemically or physically to the active ingredient or any ingredient of the drug vehicle. The authors state that it is unlikely that verapamil would be found in fibrotic scar tissue. However, treating fibrotic connective tissue is the essence of the transdermal treatment and should lead to remodeling of fibrotic tissue by retarding the production of fibroblasts at the site of injury along with the maturation of fibroblast collagenase.

Verapamil is extensively metabolized by cytochrome P450 3A4 and only 3% to 4% is excreted unchanged in the urine. Based on the reported urinary concentration of 46 ng/ml, and using data provided by Saseen et al,² the back extrapolated plasma concentration would have to be nearly 1,400 ng/ml to achieve the reported urinary concentration, and the estimated dose to produce this plasma concentration is approximately equivalent to an oral dose of 960 mg daily. The observed urinary verapamil is most likely due to contamination. Furthermore, no information is provided concerning the sensitivity and specificity of the assay. Apparently, no blank samples were run to determine if interfering substances were present in the samples. Another potential problem is site of tunica sampling and site of drug application. Based on the description, the 2 sites were not in close proximity. This study does not provide definitive evidence of lack of verapamil penetration to the tunica, and further studies are needed.

Respectfully, Robert L. Talbert, W. Jerry Easterling, William Fitch, III, University of Texas Health Science Center, 7703 Floyd Curl Dr., MSC 6220, San Antonio, Texas 78229-3900, talbert@uthscsa.edu

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References 

1. Fitch WP , Easterling WJ . Topical verapamil, trifluoperazine and magnesium sulfate for Peyronie’s disease . Int J Impot Res . 2001;13(suppl.):S62
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2. Saseen JJ , Porter JA , Barnette DJ , Bauman JL , Zajac EJ , Carter BL . Postabsorption concentration peaks with brand-name and generic verapamil: a double-blind, crossover study in elderly hypertensive patients . J Clin Pharmacol . 1997;37:526
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