Pharmacokinetics and effects of intravesical oxybutynin on the paediatric neurogenic bladder.
OBJECTIVE
To evaluate the pharmacokinetics of both oxybutynin and its active metabolite, N-desethyl oxybutynin (NDO), when the drug is instilled directly into the bladder in children with myelodysplasia and neurogenic bladder disturbance, in whom it may improve continence and decrease the risk of upper urinary tract deterioration.


METHODS
The study comprised 13 children (five girls and eight boys, mean age 9.3 years, range 1-15) with neurogenic bladders who were treated using clean intermittent catheterization and intravesical instillation of a sterile, pharmacy-produced solution of oxybutynin. Steady-state minimum plasma levels of oxybutynin and NDO, together with their effect on urodynamic variables and incontinence, were evaluated. The dose (0.04-0.17 mg/kg, mean 0.1 mg/kg) was instilled twice daily.


RESULTS
The effects of the drug on incontinence and urodynamic variables were pronounced, improving both in most cases. Minimum plasma levels were < 0.3-7.2 ng/mL for oxybutynin and 0.8-14 ng/mL for NDO. The ratio of oxybutynin to NDO was 0.29-0.83 (mean 0.47).


CONCLUSIONS
There was no clear relationship between minimum plasma levels of the drug or NDO and their clinical effects; however, the combination of oxybutynin and NDO seemed to be more strongly correlated with the clinical effects.
Amark
P
P
Department of Pediatrics, Karolinska Hospital, Stockholm, Sweden.
Eksborg
S
S
Juneskans
O
O
Bussman
G
G
Palm
C
C
D000283:Administration, Intravesical; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008333:Mandelic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010276:Parasympatholytics / Q000009:adverse effects / Q000493:pharmacokinetics*; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy / Q000378:metabolism*; D014549:Urinary Incontinence / Q000209:etiology / Q000378:metabolism; D014563:Urodynamics
D008333:Mandelic Acids; D010276:Parasympatholytics; C005419:oxybutynin