Effect of age and gender on the pharmacokinetics of R667, a novel agent for the treatment of emphysema, in healthy volunteers.
The purpose of the present study was to assess the impact of age and gender on the pharmacokinetics (PK) of R667. Thirty six healthy male and female volunteers (12 m 18-45 years; 12 m and 12 f > or = 65 years) received a single 1 mg oral dose of R667. Serial blood samples were collected for determination of plasma R667 and metabolite concentrations. The PK parameters of R667 were similar between elderly males and young males (Cmax = 9.8 vs 9.8 ng/mL; AUC(0-last) = 50.9 vs 47.3 ng x h/mL, respectively). Exposure of R667 increased in elderly females compared to elderly males (Cmax = 13.1 vs 9.8 ng/mL; AUC(0-last) = 60.8 vs 47.3 ng x h/mL, respectively). When the CL/F was corrected for BSA and V/F corrected for weight these differences were no longer evident. In conclusion these exposure differences are not considered clinically relevant, and no dose adjustment of R667 is required based on gender or age.
Brennan
B
B
Hoffmann-La Roche, Nutley, NJ, USA. Barbara.Brennan@roche.com
Chiu
Y
Y
Berthelon
L
L
Kolis
S
S
Davies
B
B
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004646:Emphysema / Q000188:drug therapy*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D012737:Sex Factors
D011720:Pyrazoles; C511499:R667 compound; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human