Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics.
OBJECTIVE
To evaluate the effects of gender, age, diabetes mellitus, renal and hepatic impairment on tadalafil pharmacokinetics and tolerability.


METHODS
Six single-dose (5, 10 or 20 mg orally) clinical pharmacology studies were conducted in the UK, Belgium, Poland and Germany in healthy male and female subjects, elderly subjects and subjects with diabetes mellitus, renal impairment, end-stage renal failure (ESRF) or hepatic impairment. The gender study also incorporated administration of 10 mg tadalafil daily for 10 days.


RESULTS
Systemic exposure in the elderly was 25% greater than in young subjects (mean AUC ratio 1.25; 90% confidence interval 0.972, 1.61). The AUC was 19% lower in subjects with diabetes mellitus than in healthy age/gender-matched controls. Pharmacokinetics in female subjects were essentially similar to those in males. Exposure in subjects with mild or moderate renal insufficiency was approximately twice that in healthy subjects. The mean AUC for the major metabolite (total methylcatechol glucuronide) in the presence of ESRF was three times the mean for healthy subjects. Haemodialysis contributed negligibly to elimination of tadalafil or the metabolite. Hepatic impairment had negligible effects on exposure. The most common adverse events in these six studies were headache, back pain and myalgia. A 10-mg dose was not well tolerated by subjects with moderate renal dysfunction in this study.


CONCLUSIONS
No clinically significant effect of gender, age, diabetes mellitus or hepatic impairment on tadalafil pharmacokinetics was observed. Renal insufficiency resulted in increased systemic exposure. Tadalafil was not associated with any serious clinically significant adverse events or study discontinuations due to adverse events.
Forgue
S Thomas
ST
Lilly Research Laboratories, Indianapolis, IN 46285, USA. s.t.forgue@lilly.com
Phillips
Diane L
DL
Bedding
Alun W
AW
Payne
Christopher D
CD
Jewell
Hayley
H
Patterson
Beverley E
BE
Wrishko
Rebecca E
RE
Mitchell
Malcolm I
MI
D000328:Adult; D000367:Age Factors; D001530:Belgium; D002243:Carbolines / Q000493:pharmacokinetics*; D003920:Diabetes Mellitus / Q000378:metabolism*; D007172:Erectile Dysfunction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005858:Germany; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism*; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics*; D011044:Poland; D012737:Sex Factors; D000068581:Tadalafil; D006113:United Kingdom
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil