Lack of age and gender effects on single‐dose pharmacokinetics of tomopenem (RO4908463/CS‐023), a novel carbapenem

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • This compound belongs to a well‐described class of antibacterials, the carbapenems, which are characterized by excellent bactericidal activity. • This compound is unique in that it has activity against methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa. • The pharmacokinetics (PK) of all molecules in this class is characterized by short plasma half‐lives and renal elimination as the major source of clearance. • Age‐ and gender‐related effects on renal and hepatic function have been shown to necessitate adjustments in dosing regimens to ensure safe and efficacious exposures to drugs. WHAT THIS STUDY ADDS • The extent of changes in PK of tomopenem in the elderly and women is minor when compared with healthy male volunteers, so dose adjustments are not necessary. • Instead of age or gender, creatinine clearance can be used to explain the slight effect of these variables on PK. AIMS 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.