Aim: To study the influence of chronological age on fentanyl permeation through human skin in vitro using static diffusion cells. Elderly individuals are known to be more sensitive to opioids and obtain higher plasma concentrations following dermal application of fentanyl compared to younger individuals. The influence of age - as an isolated pharmacokinetic term - on the absorption of fentanyl has not been previously studied. Method: Human skin from 30 female donors was mounted in static diffusion cells, and samples were collected during 48 h. Donors were divided into three age groups: <30 years of age (n = 6), ≥30 and <60 years of age (n = 18) and ≥60 years of age (n = 6). Results: The youngest group had a significantly higher mean absorption (3,100 ng/cm2) than the two other groups (2,000 and 1,475 ng/cm2, respectively) and a significant larger AUC (young age group: 9,393 ng; middle and old age groups: 5,922 and 4,050 ng, respectively). Furthermore, the lag time and absorption rate were different between the three groups, with a significantly higher rate in the young participants versus the oldest participants. Conclusion: We demonstrate that fentanyl permeates the skin of young individuals in greater amounts and at a higher absorption rate than in middle-aged and old individuals in vitro.

1.
Neerken S, Lucassen GW, Bisschop MA, Lenderink E, Nuijs TA: Characterization of age-related effects in human skin: a comparative study that applies confocal laser scanning microscopy and optical coherence tomography. J Biomed Opt 2004;9:274-281.
2.
Li L, Mac-Mary S, Marsaut D, Sainthillier JM, Nouveau S, Gharbi T, et al: Age-related changes in skin topography and microcirculation. Arch Dermatol Res 2006;297:412-416.
3.
Ghadially R, Brown BE, Sequeira-Martin SM, Feingold KR, Elias PM: The aged epidermal permeability barrier. Structural, functional, and lipid biochemical-abnormalities in humans and a senescent murine model. J Clin Invest 1995;95:2281-2290.
4.
Seyfarth F, Schliemann S, Antonov D, Elsner P: Dry skin, barrier function, and irritant contact dermatitis in the elderly. Clin Dermatol 2011;29:31-36.
5.
Rogers J, Harding C, Mayo A, Banks J, Rawlings A: Stratum corneum lipids: the effect of ageing and the seasons. Arch Dermatol Res 1996;288:765-770.
6.
Christophers E, Kligman AM: Percutaneous Absorption in Aged Skin. New York, Pergamon Press, 1964.
7.
Kligman AM: Perspectives and problems in cutaneous gerontology. J Invest Dermatol 1979;73:39-46.
8.
Roskos KV, Guy RH, Maibach HI: Percutaneous absorption in the aged. Dermatol Clin 1986;4:455-465.
9.
Roskos KV, Maibach HI: Percutaneous absorption and age. Implications for therapy. Drugs Aging 1992;2:432-449.
10.
Roskos KV, Maibach HI, Guy RH: The effect of aging on percutaneous absorption in man. J Pharmacokinet Biopharm 1989;17:617-630.
11.
Kobayashi H, Tagami H: Functional properties of the surface of the vermilion border of the lips are distinct from those of the facial skin. Br J Dermatol 2004;150:563-567.
12.
Tagami H: Functional characteristics of the stratum corneum in photoaged skin in comparison with those found in intrinsic aging. Arch Dermatol Res 2008;300:S1-S6.
13.
Gniadecka M, Jemec GB: Quantitative evaluation of chronological ageing and photoageing in vivo: studies on skin echogenicity and thickness. Br J Dermatol 1998;139:815-821.
14.
Kaestli LZ, Wasilewski-Rasca AF, Bonnabry P, Vogt-Ferrier N: Use of transdermal drug formulations in the elderly. Drugs Aging 2008;25:269-280.
15.
Wilder-Smith OHG: Opioid use in the elderly. Eur J Pain 2005;9:137-140.
16.
Mercadante S, Arcuri E: Pharmacological management of cancer pain in the elderly. Drugs Aging 2007;24:761-776.
17.
Holdsworth MT, Forman WB, Killilea TA, Nystrom KM, Paul R, Brand SC, et al: Transdermal fentanyl disposition in elderly subjects. Gerontology 1994;40:32-37.
18.
DrugBank - Open Data Drug & Drug Target Database, 2012.
19.
LOGKOW - A databank of evaluated octanol-water partition coefficients (Log P), 2012.
20.
Varvel JR, Shafer SL, Hwang SS, Coen PA, Stanski DR: Absorption characteristics of transdermally administered fentanyl. Anesthesiology 1989;70:928-934.
21.
Bronaugh RL, Stewart RF, Simon M: Methods for in vitro percutaneous absorption studies. VII. Use of excised human skin. J Pharm Sci 1986;75:1094-1097.
22.
Nielsen JB, Plasencia I, Sorensen JA, Bagatolli LA: Storage conditions of skin affect tissue structure and subsequent in vitro percutaneous penetration. Skin Pharmacol Physiol 2011;24:93-102.
23.
Nielsen JB: Percutaneous penetration through slightly damaged skin. Arch Dermatol Res 2005;296:560-567.
24.
Lambropoulos J, Spanos GA, Lazaridis NV, Ingallinera TS, Rodriguez VK: Development and validation of an HPLC assay for fentanyl and related substances in fentanyl citrate injection, USP. J Pharm Biomed Anal 1999;20:705-716.
25.
Bayer A, Tadd W: Unjustified exclusion of elderly people from studies submitted to research ethics committee for approval: descriptive study. BMJ 2000;321:992-993.
26.
Crome P, Lally F, Cherubini A, Oristrell J, Beswick AD, Clarfield AM, et al: Exclusion of older people from clinical trials: professional views from nine European countries participating in the PREDICT study. Drugs Aging 2011;28:667-677.
27.
McLachlan AJ, Bath S, Naganathan V, Hilmer SN, Le Couteur DG, Gibson SJ, Blyth FM: Clinical pharmacology of analgesic medicines in older people: impact of frailty and cognitive impairment. Br J Clin Pharmacol 2011;71:351-364.
28.
Kornick CA, Santiago-Palma J, Moryl N, Payne R, Obbens E: Benefit-risk assessment of transdermal fentanyl for the treatment of chronic pain. Drug Saf 2003;26:951-973.
29.
Clark AJ, Ahmedzai SH, Allan LG, Camacho F, Horbay GLA, Richarz U, Simpson K: Efficacy and safety of transdermal fentanyl and sustained-release oral morphine in patients with cancer and chronic non-cancer pain. Curr Med Res Opin 2004;20:1419-1428.
30.
Cepeda MS, Farrar JT, Baumgarten M, Boston R, Carr DB, Strom BL: Side effects of opioids during short-term administration: effect of age, gender, and race. Clin Pharmacol Ther 2003;74:102-112.
31.
Hilmer SN, McLachlan AJ, Le Couteur DG: Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol 2007;21:217-230.
32.
Meidan VM, Roper CS: Inter- and intra-individual variability in human skin barrier function: a large scale retrospective study. Toxicol In Vitro 2008;22:1062-1069.
33.
Roskos KV, Guy RH: Assessment of skin barrier function using transepidermal water loss: effect of age. Pharm Res 1989;6:949-953.
34.
Grond S, Radbruch L, Lehmann KA: Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl. Clin Pharmacokinet 2000;38:59-89.
35.
Farahmand S, Maibach HI: Transdermal drug pharmacokinetics in man: interindividual variability and partial prediction. Int J Pharm 2009;367:1-15.
36.
Gloth FM: Pain management in older adults: prevention and treatment. J Am Geriatr Soc 2001;49:188-199.
37.
Konda S, Meier-Davis SR, Cayme B, Shudo J, Maibach HI: Age-related percutaneous penetration part 2: effect of age on dermatopharmacokinetics and overview of transdermal products. Skin Therapy Lett 2012;17:5-7.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.