Aims
of Study
Oral oxybutynin, a valuable detrusor spasmolytic, is bedevilled by unpleasant
side effects. Several reports indicate that intravesical oxybutynin
is efficacious and lacks side effects in adults but no consistent
urodynamic and pharmacokinetic patterns are evident. In this report,
the urodynamic effects and pharmacokinetics of oxybutynin are described
for ten spinal cord injury patients with detrusor hyperreflexia who
received oral, intravesical passive diffusion (PD) and
intravesical electromotive drug administration (EMDA) single doses
of drug. Both sets of measurements are correlated to the methods of
administration, therapeutic efficacy and anticholinergic side effects.
Methods
The
study plan included six, 8 hour urodynamic sessions at weekly intervals
in order to monitor the following situations applied randomly: (a) no treatment, (b) oral oxybutynin 5 mg, (c)
intravesical 100 ml NaCl 0.9% x 60 min,
(d) intravesical oxybutynin 5 mg in 100 ml NaCl 0.45% x 60 min,
(e) intravesical 100 ml NaCl 0.9% with 5 mA x 30 min, (f) intravesical 5 mg oxybutynin in 100
ml NaCl 0.45% with 5 mA x 30 min. Each treatment was associated with
periodic blood and bladder content sampling. During the study period
patients were free from urinary infection and not receiving any drug
that influenced detrusor and striated sphincter behavior. The occurence
of local or systemic adverse effects was noted. Differences among
group means were analyzed by ANOVA.
Results
The
following data were analysed: number, maximum amplitude and duration
of uninhibited detrusor contractions and urine volume residual (Table
1). There was subjective but no significant objective improvement
over baseline with oral and intravesical PD oxybutynin. Conversely
there was significant improvement in all objective urodynamic measurements
with intravesical EMDA oxybutynin. Plasma profiles were a single
peak and decay following oral oxybutynin and two distinct peaks with
both intravesical PD and EMDA oxybutynin. AUC/8 h: intravesical PD
709 ng vs oral 1485 ng (p <0.005) vs intravesical EMDA 2781 ng
(p < 0.001). Bladder
content samples confirmed oxybutynin absorption. Oral oxybutynin caused
anticholinergic side effects in 6/10 patients. There were no side
effects with intravesical PD or EMDA administrations.
Table 1. Urodynamic outcomes. Data are the
means ± SEM of 10 observations per group.
|
|
Uninhibited
Detrusor Contractions
|
Urine
Volume Residual
|
|
UDM
|
Number
|
Amplitude
cm
H2O
|
Duration
sec
|
4
h
ml
|
8
h
ml
|
|
(a)
|
33.6
± 7.2
|
64.1
± 9.0
|
689.4
± 406.7
|
36.2
± 19.2
|
48.7
± 31.2
|
|
(b)
|
25.1
± 6.2
|
60.5
± 10.2
|
559.3
± 283.2
|
41.0
± 31.4
|
43.0
± 21.3
|
|
(c)
|
27.4
± 6.2
|
65.4
± 9.2
|
671.9
± 508.4
|
42.8
± 23.1
|
36.2
± 23.6
|
|
(d)
|
21.9
± 7.8
|
58.2
± 8.8
|
574.2
± 345.4
|
43.5
± 25.1
|
47.8
± 21.9
|
|
(e)
|
35.6
± 9.0
|
57.0
± 7.3
|
664.7
± 567.1
|
44.3
± 22.8
|
45.7
± 12.2
|
|
(f)
|
9.2
± 3.7
|
35.7
± 10.5
|
265.1
± 131.0
|
235.2
± 110.7
|
237.5
± 129.5
|
|
P value
|
0.0006
|
0.0049
|
0.0521
|
0.011
|
0.015
|
Conclusions
Intravesical
oxybutynin is a valid route of delivery and, although accelerated
intravesical administration (EMDA) leads to significantly higher plasma
levels, the side effects seen with oral oxybutynin do not occur.
