[Pharmacological evaluation of efficacy and safety of propiverine hydrochloride in patients of overactive bladder--relationship between urodynamic observation and propiverine pharmacokinetics--].
OBJECTIVE
The clinical benefit of propiverine hydrochloride against overactive bladder was evaluated, and the relationships between urinary voiding functions and the pharmacokinetics were investigated by means of clinical pharmacology with PK/PD approach.


METHODS
Total 7 patients suffering urgency with urinary frequency and incontinence received propiverine hydrochloride in doses of 10 mg qd or 20 mg qd for 4 weeks, and then the doses were switched in cross-over manner to continue the treatment for further 4 weeks. The urodynamic measurements as well as pharmacokinetic samplings were done before the medication, 4 weeks and 8 weeks after the starting medication, to examine the dose-response and concentration-response relationships.


RESULTS
The volume at first desire to void increased according to dose increased, and the volume at first involuntary contraction tended to increase according to both dose and drug concentration in plasma. However, no apparent dose-response relationships were observed for maximum urinary flow rate and the detrusor pressure at the maximum urinary flow rate. The PK/PD analysis using Emax model suggested that, approximately 75 ng/mL of the propiverine concentration in plasma allowed the increase in the volume at first involuntary contraction for 50%. The urinary residual volume increased in dose-dependent manner only in the patients with severe grade of lower urinary tract obstruction, but scarcely increased in the patients with moderate grade or below.


CONCLUSIONS
Propiverine hydrochloride improved the urinary voiding functions with a tendency to depend on both dose and concentration in plasma. After the administration of propiverine hydrochloride, the concentration in plasma will immediately reach the level at which the drug can increase in the volume at first involuntary contraction for 50%, and then the concentration level will sustain the effect ranging from 10% to 50% increase in bladder volume. Furthermore, the lower urinary tract obstruction will be a predictor of increase in urinary residual volume.
Sugiyama
Takahide
T
Department of Urology, Kinki University School of Medicine.
Shimizu
Nobutaka
N
Hashimoto
Kiyoshi
K
Yoshioka
Nobuhiro
N
Hanai
Tadashi
T
Matsumoto
Seiji
S
Uemura
Hirotsugu
H
D000368:Aged; D001561:Benzilates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010276:Parasympatholytics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000503:physiopathology; D014549:Urinary Incontinence / Q000188:drug therapy / Q000503:physiopathology; D014555:Urination Disorders / Q000188:drug therapy* / Q000503:physiopathology; D014563:Urodynamics / Q000502:physiology
D001561:Benzilates; D010276:Parasympatholytics; C015586:propiverine