Lack of age and gender effects on single-dose pharmacokinetics of tomopenem (RO4908463/CS-023), a novel carbapenem.
OBJECTIVE
To investigate the effect of age and gender on the tolerability, safety and pharmacokinetics (PK) of tomopenem (RO4908463/CS-023), a novel carbapenem antibiotic, and its major metabolite.


METHODS
Forty-two subjects were assigned to one of the following three groups: young men, elderly men and elderly women. The PK, safety and tolerability of an intravenous infusion of 1500 mg tomopenem and its resultant major metabolite (open beta-lactam ring) were assessed.


RESULTS
Minor differences in exposure of both tomopenem and the major metabolite were seen. The area under the curve (AUC) of tomopenem was 22% higher in elderly men compared with young men, and 19% higher in elderly women relative to the elderly men. Total clearance of tomopenem decreased with decreasing creatinine clearance. In the two male groups, renal clearance values of tomopenem were similar (3.52 and 3.67 l h(-1)) and higher than in the elderly female group (2.83 l h(-1)). The mean half-lives ranged from 2.03 (healthy young men) to 2.41 h (elderly men). The difference in AUC of tomopenem can be explained by differences in the mean creatinine clearances of 116 (young men), 101 (elderly men) and 84.7 (elderly women) ml min(-1) 1.73 m(-2), respectively.


CONCLUSIONS
While some PK parameters were statistically different among the three groups, the differences were mostly minor and unlikely to be clinically meaningful. The difference in the PK can be largely attributed to the difference in creatinine clearance of these groups.
Department of Clinical Pharmacology, Roche, Nutley, NJ 07110, USA. navita_l.mallalieu@roche.com
Navita L
NL
Mallalieu
Siân
S
Lennon
Thorold
T
Guy
Mei
M
Liu
Eric
E
Luedin
Brian E
BE
Davies
D000328:Adult; D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012737:Sex Factors; D016896:Treatment Outcome; D055815:Young Adult
D015780:Carbapenems; C492232:tomopenem