The Development of Transdermal Ketamine Patch
Main Article Content
Abstract
Objective
We prepared the transdermal ketamine patch, determined the size of the patch to yield proper plasma ketamine level due to human skin permeability and the amount of residual ketamine in the patch, and estimated the utility of this ketamine transdermal patch when it will be applied to patients.
Methods
A ketamine patch was prepared with ketamine hydrochloride intramuscular solution (3.0mg/cm2). The ketamine patch was put on the skin samples taken from the human. The solutions of the diffusion cell were examined every two hours after the application until 30 hours. The amount of ketamine that has penetrated into the skin was measured by using HPLC system, and Flux of transdermal ketamine patch was defined.
Results
The cumulative ketamine permeation amount was found to be 785.6 mg/cm2 at the 30-hour sampling, showing a stable Flux of 30.1 mg/cm2/hr during the period from 10 to 30 hours of sampling.
Conclusion
We have been attempting to formulate transdermal ketamine patches at a size of 155 cm2 to yield a plasma ketamine level of 50 ng/mL for use in the clinical practice setting. The patch may become a formulation of choice as an analgesic adjuvant for combined use with opioids.
Article Details
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References
1. Kaneuchi M, Sawaguchi R, Kohri N, Senbongi K, Sakai H, Asano M, Iseki K. Evaluation of preparation of ketamine in hospital for practical use analysis of plasma concentration profiles of ketamine and norketamine after oral administration.JJSPC 2006; 13(1): 18-21.
2. Kirby T. Ketamine for depression: the hights and lows. The Lancet Psychiatry 2015;2(9):783-784.
3. Malhi GS, Byrow Y, Cassidy F, Cipriani A, Demyttenaere K, et al. Ketamine: stimulating antidepressant treatment? Br J Psychiatry Open 2016;2(3) e5-e9.
4. Kubota R, Komiyama T, Miwa Y, Bun S, Ishii J, Minei S, Irie A. Pharmacokinetics of ketamine and norketamine after oral administration of a liquid formulation of ketamine. J Curr Surg 2013;3(2):82-86.
5. Tsukamoto A. Clinical application of the hospital compounding of transdermal ketamine. Tokyo, Japan: Kitasato University; 1999. Thesis.
6. Azevedo VM, Lauretti GR, Pereira NL, Reis MP. Transdermal ketamine as an adjuvant for postoperative analgesia after abdominal gynecological surgery using lidocaine epidural blockade. Anesth Analg 2000;91(6):1479-1482.
7. Bolze S, Boulieu R. HPLC determination of ketamine, norke- tamine, and dehydronorketamine in plasma with high-purity reverse-phase sorbent. Clin Chem 1998;44(3):560- 564.
8. Yanagihara Y, Ohtani M, Kariya S, Uchino K, Hiraishi T, Ashizawa N, Aoyama T, Yamamura Y, Yamada Y and Iga T. Plasma Concentration Profiles of Ketamine and Norketamine after Administration of Various Ketamine Preparations to Healthy Japanese Volunteers. Biopharmaceutics & Drug disposition 2003; 24:37-43.
9. Sato T, Kataoka T, Shino M, Nishizaki H, Adachi I. Effect of oral ketamine on neuropathic pain. Palliative Care Research 2008; 3(1): 216-220.
10. Ushida T, Tani T, Kanbara T, et al. Analgesic Effects of Ketamine Ointment in Patients With Complex Regional Pain Syndrome Type1. Regional anesthesia and pain medicine 2002; 27(5): 524-528.
11. Reich DL, Siivay G. Ketamine; an update on the 1st 25 years of clinical experience. Can J Anaesth 1989; 36: 186-197.
12. Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain 1999; 82: 111-125.
13. Persson J, Hasselstrom J, Wirlund B, Heller A, Svensson JO, Gustafsson LL. The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans. Acta Anaesthesiol. Scand. 1998; 42: 750– 758
14. Yajima C, Arita E, Hanaoka K. Chronic pain and ketamine. Pain Clinic 1999; 20(8): 1134-1142 (in Japanese)
15. Roy SD, Flynn GL. Transdermal delivery of narcotic analgesics: pH, anatomical, and subject influences on cutaneous permeability of fentanyl and sufentanil. Pharm Res 1990;7(8):842- 847.
16. Sebel PS, Barrett CW, et al. Transdermal absorption of fentanyl and sufentanil in man. Eur J Clin pharmacol 1987;32:529-531.
17. Watabe T. The present conditions and the prospects of a skin application drug. Drug Delivery System 2007;22:450- 457.