title: Pharmacokinetics of ertapenem in healthy young volunteers.
abstract: Ertapenem (INVANZ) is a new once-a-day parenteral beta-lactam antimicrobial shown to be effective as a single agent for treatment of various community-acquired and mixed infections. The single- and multiple-dose pharmacokinetics of ertapenem at doses up to 3 g were examined in healthy young men and women volunteers. Plasma and urine samples collected were analyzed using reversed-phase high-performance liquid chromatography with UV detection. Ertapenem is highly bound to plasma protein. The protein binding changes from approximately 95% bound at concentrations of <50 micro g/ml to approximately 92% bound at concentrations of 150 micro g/ml (concentration at the end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than dose proportional increase in the area under the curve from 0 h to infinity (AUC(0- infinity )) of total ertapenem. The single-dose AUC(0- infinity ) of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem in plasma ranged from approximately 145 to 175 micro g/ml at the end of a 30-min infusion, from approximately 30 to 34 micro g/ml at 6 h, and from approximately 9 to 11 micro g/ml at 12 h. The mean plasma t(1/2) ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CL(P)) was via renal clearance. The remainder of the CL(P) was primarily via the formation of the beta-lactam ring-opened metabolite that was excreted in urine. There were no clinically significant differences between the pharmacokinetics of ertapenem in men and women. Ertapenem does not accumulate after multiple once-daily dosing.
authors.affiliation: Merck Research Laboratories, West Point. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19486, USA. anup_majumdar@Merck.com
authors.forename: A K
authors.initials: AK
authors.lastname: Majumdar
authors.forename: D G
authors.initials: DG
authors.lastname: Musson
authors.forename: K L
authors.initials: KL
authors.lastname: Birk
authors.forename: C J
authors.initials: CJ
authors.lastname: Kitchen
authors.forename: S
authors.initials: S
authors.lastname: Holland
authors.forename: J
authors.initials: J
authors.lastname: McCrea
authors.forename: G
authors.initials: G
authors.lastname: Mistry
authors.forename: M
authors.initials: M
authors.lastname: Hesney
authors.forename: L
authors.initials: L
authors.lastname: Xi
authors.forename: S X
authors.initials: SX
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Haesen
authors.forename: R A
authors.initials: RA
authors.lastname: Blum
authors.forename: R L
authors.initials: RL
authors.lastname: Lins
authors.forename: H
authors.initials: H
authors.lastname: Greenberg
authors.forename: S
authors.initials: S
authors.lastname: Waldman
authors.forename: P
authors.initials: P
authors.lastname: Deutsch
authors.forename: J D
authors.initials: JD
authors.lastname: Rogers
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000077727:Ertapenem; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007769:Lactams; D008297:Male; D011485:Protein Binding; D012727:Sex Characteristics; D013056:Spectrophotometry, Ultraviolet; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D007769:Lactams; D047090:beta-Lactams; D000077727:Ertapenem