Pharmacokinetics of ertapenem in healthy young volunteers.
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.
Majumdar
A K
AK
Merck Research Laboratories, West Point. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19486, USA. anup_majumdar@Merck.com
Musson
D G
DG
Birk
K L
KL
Kitchen
C J
CJ
Holland
S
S
McCrea
J
J
Mistry
G
G
Hesney
M
M
Xi
L
L
Li
S X
SX
Haesen
R
R
Blum
R A
RA
Lins
R L
RL
Greenberg
H
H
Waldman
S
S
Deutsch
P
P
Rogers
J D
JD
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
D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D007769:Lactams; D047090:beta-Lactams; D000077727:Ertapenem