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Incontinence and Overactive Bladder
The Safety and Efficacy of Transdermal Oxybutynin in the
Management of Overactive Bladder
a report by
Koritsiadis G Sotirios,
Koritsiadis S George
and Stravodimos Konstandinos
1. Urology Department, Nikaia General Hospital, Piraeus; 2. 1st Department of Urology, School of Medicine, National and Kapodistrian University of Athens
Overactive bladder (OAB) is a complex syndrome defined as “urgency cholinergic contractions in the ileum, with the latter receptors assuming
with or without urge incontinence usually with frequency and nocturia” a greater role.
The major limitation of pharmacotherapy for OAB is
in the absence of infection or other proven pathology.
OAB affects the significant incidence of anticholinergic side effects due to the
33 million Americans,
with an overall prevalence of 16.5%; 16.9% of antagonism of these receptors.
women and 16.0% of men are affected, and prevalence increases with
age among both genders.
The EPIC study showed that OAB patients Oxybutinin (OXY) has been used for the treatment of OAB for almost
have impaired quality of life, higher rates of depression and decreased 30 years in different forms, such as immediate-release (IR) and extended-
enjoyment of sexual activity, while a combination of OAB with lower release (ER), while different delivery methods have been used to avoid
urinary tract symptoms aggravates all symptoms.
The pathophysiology of first-pass hepatic metabolism and minimise side effects.
bladder overactivity is still obscure and includes idiopathic cases, administration, OXY is metabolised by the cytochrome P450 in the liver,
neurological illness, bladder outlet obstruction, emergence of new as well as in the gastrointestinal tract. The final bioavailability of the drug
voiding reflexes in pathological conditions and, possibly, hormonal is only around 6%; however, the end product of the metabolism process
factors, as recently suggested.
is N-desethyloxybutynin (N-DEO), which achieves four to 10 times higher
levels in plasma than the native substance.
N-DEO is more potent than
There are various management strategies for OAB, with behavioural OXY and binds with higher affinity to MRs in the salivary gland.
therapy as first-line treatment (pelvic-floor muscle exercise), fluid
restriction, pelvic-floor electrical stimulation, dietary modification, timed Delivering OXY through the skin means that its metabolism to N-DEO is
voiding and, finally, pharmacotherapy, which is the most popular and avoided, since the epidermis contains <5% of the body’s P450.
It is known that activation of muscarinic receptors (MRs) on Transdermal OXY (OXY-TDS) is composed of three layers with a total
detrusor muscles is one of the leading mechanisms in the genesis of surface area of 39cm
containing 36mg racemic OXY, designed to
abnormal detrusor contractions.
Five MR subtypes have been identified continuously deliver OXY over a three- to four-day wear period. The first
(M1–M5), and their distribution varies according the organ system in layer consists of a polyester/ethylene–vinyl acetate film that helps to
which they are expressed. In the bladder, the most abundant receptor maintain skin hydration, which facilitates the penetration and
subtype is M2, followed by M3, which is also responsible for OAB absorption of OXY through the layers of the skin. The second layer is an
symptoms since it is the receptor that mediates detrusor contraction.
M1 adhesive acrylic film that contains the active component, along with
receptors are primarily facilitatory, whereas M2 receptors are primarily triacetin (a skin permeation enhancer). The third layer consists of two
inhibitory; together with M4 receptors, these receptors modulate detrusor overlapping silicone-coated polyester strips that are taken off by the
contraction through the release of mediators from the urothelium.
patient before use.
MRs are activated by parasympathetic cholinergic nerves that release Appell et al. investigated the metabolism of OXY and saliva output in 13
acetylcholine. In the salivary gland, secretion of saliva is mediated healthy subjects in a two-way cross-over study after OXY-TDS and
through M3 and, to a lesser extent, M1 receptors.
In the extended-release oral oxybutynin. In this study, steady-state plasma
gastrointestinal tract, M2 and M3 receptors participate in mediating concentrations were achieved after the first transdermal application; in
contrast, the oral OXY form needed a second dose to reach steady state.
In addition, plasma concentrations were less variable in the OXY-TDS
Koritsiadis G Sotirios is a Consultant Urologist in the
Urology Department at Nikaia General Hospital in Piraeus,
group. Furthermore, N-DEO levels were considerably lower in the
a position he has held since 2003. He has been a Fellow OXY-TDS group, and this was correlated to a higher saliva output.
of the European Board of Urology (FEBU) since 1992,
and is a member of the Endourology Society and the
International Continence Society (ICS). He specialises in
OXY is a tertiary amine with an antimuscarinic and spasmolytic mode of
urinary tract ultrasound, and is the author of a manual
action. It exists in two forms: R-and S-enantiomers (R-OXY and S-OXY,
focusing on ultrasound anatomy and pathology of the
lower urinary tract, as well as several publications,
respectively). R-OXY has greater anticholinergic activity compared with
abstracts and books. Dr Sotirios received his MD from the University of Athens and S-OXY, but spasmolytic activity is equal for both. Zobrist et al. examined
completed his urological training at the Evaggelismos General Hospital in 1979. As a
the pharmacokinetics of the enantiomers R- and S- after TSD and oral
urological registrar, he trained in neurology and urodynamics at Freeman Hospital in
Newcastle from 1982 to 1983, and received certification of full registration in endoscopic
administration in 16 healthy female and male subjects. The investigators
surgery and surgical techniques.
found that the TDS system delivered OXY in a continuous manner, in
which both plasma R- and S-OXY increased rapidly but remained stable
for approximately 96 hours thereafter. R- and S-DEO followed the same
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