Tolerability and steady-state pharmacokinetics of terodiline and its main metabolites in elderly patients with urinary incontinence.
The elderly form an important target group for the treatment of urinary urge incontinence with drugs such as terodiline (Mictrol, Terolin). In order to evaluate its steady-state pharmacokinetics and tolerability in geriatric patients terodiline 12.5 mg b.d. was given to 28 hospitalized patients with urinary incontinence (mean age 85 years) for six weeks. The patients were monitored during the study and for 6 weeks afterwards, blood samples being taken at regular intervals. In addition to these multi-diseased and polymedicated patients, a small, homogenous group of healthy volunteers (mean age 40 years) was studied as a reference group, being given terodiline 12.5 mg b.d. for 2 weeks. Terodiline was generally well tolerated by the patients and no significant change in blood pressure or heart rate were found. One patient was withdrawn due to adverse effects. The mean terminal half-life of terodiline was 131 h and the clearance after oral administration (clearance/systemic availability) was 39 ml.min-1. The corresponding figures for the healthy volunteers were 57 h and 75 ml.min-1. The average steady-state serum concentration was 518 micrograms.l-1 in the geriatric patients and 238 micrograms.l-1 in the healthy volunteers. Steady-state was reached within 3 weeks in 20 of the 28 patients and within 5 weeks in 7 patients. In the geriatric patients the steady-state serum concentration of the main metabolite p-hydroxyterodiline, during the last three weeks on terodiline was 45 micrograms.l-1, 57 micrograms.l-1, and 45 micrograms.l-1, respectively, and a similar value was found in the healthy volunteers, 47 micrograms.l-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Hallén
B
B
Department of Pharmacokinetics and Metabolism, R & D, Kabi, Stockholm, Sweden.
Bogentoft
S
S
Sandquist
S
S
Strömberg
S
S
Setterberg
G
G
Ryd-Kjellén
E
E
D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D002082:Butylamines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010276:Parasympatholytics / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D014549:Urinary Incontinence / Q000188:drug therapy*
D002082:Butylamines; D010276:Parasympatholytics; C010637:terodiline