Treatment of overactive bladder in the aging population: focus on darifenacin

Figures & data

Table 1 Distribution of muscarinic receptors

Subtypes	Distribution
M1	Brain (cortex, hippocampus), sympathetic ganglia, glands
M2	Heart, smooth muscle, hindbrain
M3	Smooth muscle, glands, brain
M4	Brain (forebrain, striatum)
M5	Brain (substantia nigra), eye

Table 2 Affinity (pKi) of antimuscarinic compounds for the human recombinant receptor subtypes M₁– M₅ (Anderson 2006) (Mean)

	M1	M2	M3	M4	M5
Darifenacin	8.2	7.4	9.1	7.3	8.0
Oxybutynin	8.7	7.8	8.9	8.0	7.4
Tolteridine	8.8	8.0	8.5	7.7	8.0
Propiverine	6.6	5.4	6.4	6.0	6.5
Trospium	9.1	9.2	9.3	9.0	8.6

Table 3 Comparison of M₃:M₁ selectivity of the antimuscarinic compounds (Napier and Gupta 2002)

	M3 versus M1	P
Darifenacin	9.3	<0.001
Tolteridine	0.6a	<0.05
Oxybutynin	1.5b	<0.05
Propiverine	0.6a	<0.05
Trospium	1.5	NS

Notes: ^aSignificant selectivity for M₁, but unlikely to be biologically significant;

^b Significant, but unlikely to be biologically relevant.

Table 4 Outcomes comparing darifenacin or matched placebo after 12 weeks of treatment (Chapple et al 2005)

	Darifenacin(%) (7.5 mg QD)	Placebo (%)	Darifenacin(%) (15 mg QD)	Placebo (%)
Incontinence episodes/week	−8.8(−68.4)*	−7(−53.8)	−10.6(−76.8)**	7.5 (−58.3)
Incontinence episodes resulting in pad change	−4(−77.1)	−2(−47.7)	−4.8(−78.6)**	−2.7(−55.1)
Frequency of urgency/day	−2(−29)**	−1(−14.3)	−2.3(−29)**	−1.2(−16.7)
Micturition Frequency/day	−1.6(−16.6)**	−0.9(−9.1)	−1.9(−17.4)**	−1(−9.9)
Bladder capacity (mean vol void:ml)	15.4(9.6)*	7.6(4.9)	26.9(17.5)**	5.9(3.9)
Severity of urgency	−7.8(−14.2)**	−4.2(−7.8)	−9.3(−16.1)**	−4.5(−8)

Notes: Results expressed as median (%) change from baseline, at week 12;

* p<0.01;

** p<0.001 (Wilcoxon rank-sum test).

Table 5 Comparison of 2 weeks treatment outcomes of darifenacin, oxybutynin, or placebo (Zinner et al 2005)

	Darifenacin (n=58) 15 mg QD	Oxybutynin (n=58) 5 mg TDS	Placebo (n=58)
Micturition/day	9.33	9.24	9.62
Incontinence episodes/week	10.93*	9.45*	14.64
Urgency episodes/day	7.95*	8.12*	8.71
Severity of urgency episode^Table Footnote**	1.93*	1.89*	2.03

Notes: Evaluable patients (n=58). Values shown are means adjusted for sequence and period from the crossover analysis of variance;

* p<0.05 vs placebo, accounting from multiplicity by least significant difference method;

** 1=mild, 2=moderate, 3=severe.

Abbreviations: QD, once daily; TDS, three times daily

Table 6 Outcome following 12 weeks of treatment in elderly patients (Foote et al 2005)

Efficacy parameters	Darifenicin (7.5 mg QD)	Placebo	Darifenacin (15 mg QD)	Placebo
Micturitions/day	−1.8(−18.2)	−0.6(−6.5)	−1.8(−16.9)	−1.0(−9.1)
Incontinence episodes/week	−11.2(−66.7)	−4.8(−34.8)	−10.8(−75.9)	−6.8(−44.8)
Number of urgency episodes/day	−2.1(−25.7)	−0.6(−6.6)	−2.4(−25.7)	−0.8(−10.4)
Bladder capacity (mean vol voided mls)	14(10.4)	2(1.3)	27(18.0)	2(1.3)

Notes: Results expressed as median (%) change from baseline to week 12; p<0.05 in improving all four efficacy parameters (Wilcoxon rank-sum test, stratified by study).

Abbreviations: QD, once daily.

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