title: Pharmacokinetics of total and unbound ertapenem in healthy elderly subjects.
abstract: Ertapenem is a new once-a-day parenteral carbapenem antimicrobial agent. The pharmacokinetics of unbound and total concentrations of ertapenem in plasma were investigated in elderly subjects and compared with historical data from young adults. In a single- and multiple-dose study, healthy elderly males and females (n = 14) 65 years old or older were given a 1-g intravenous (i.v.) dose once daily for 7 days. Plasma and urine samples collected for 24 h on days 1 and 7 following administration of the 1-g doses were analyzed by reversed-phase high-performance liquid chromatography. Areas under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) for elderly females and males were similar following administration of 1-g single i.v. doses, and thus, the genders were pooled in subsequent analyses. Concentrations in plasma and the half-life of ertapenem were generally higher and longer, respectively, in elderly subjects than in young adults. The mean AUC(0- infinity ) of total ertapenem in the elderly was 39% higher than that in young subjects following administration of a 1-g dose. The differences were slightly greater for the mean AUC(0- infinity ) of unbound ertapenem (71%). The unbound fraction of ertapenem in elderly subjects ( approximately 5 to 11%) was generally greater than that in young adults ( approximately 5 to 8%). As in young adults, ertapenem did not accumulate upon multiple dosing in the elderly. The pharmacokinetics of ertapenem in elderly subjects, while slightly different from those in young adults, do not require a dosage adjustment for elderly patients.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania 19486, USA. don_musson@merck.com
authors.forename: D G
authors.initials: DG
authors.lastname: Musson
authors.forename: A
authors.initials: A
authors.lastname: Majumdar
authors.forename: S
authors.initials: S
authors.lastname: Holland
authors.forename: K
authors.initials: K
authors.lastname: Birk
authors.forename: L
authors.initials: L
authors.lastname: Xi
authors.forename: G
authors.initials: G
authors.lastname: Mistry
authors.forename: D
authors.initials: D
authors.lastname: Sciberras
authors.forename: J
authors.initials: J
authors.lastname: Muckow
authors.forename: P
authors.initials: P
authors.lastname: Deutsch
authors.forename: J D
authors.initials: JD
authors.lastname: Rogers
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015780:Carbapenems / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood; D000077727:Ertapenem; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007769:Lactams / Q000493:pharmacokinetics*; D008297:Male; D013056:Spectrophotometry, Ultraviolet; D047090:beta-Lactams
chemical_list: D015780:Carbapenems; D007769:Lactams; D047090:beta-Lactams; D003404:Creatinine; D000077727:Ertapenem