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Publications (4)16.54 Total impact

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    ABSTRACT: Ertapenem is a parenteral beta-lactam carbapenem antibiotic. This open-label study examined the pharmacokinetics of single 1-g intravenous doses of ertapenem, administered over 30 minutes, in patients with mild, moderate, and advanced renal insufficiency (RI) and in patients with end-stage renal disease (ESRD) requiring hemodialysis. Pharmacokinetics were compared with historical controls pooled across healthy young and elderly subjects. Area under the concentration-time curve from time zero to infinity increased 7% in mild, 53% in moderate, 158% in advanced RI, and 192% in ESRD; end of infusion concentration changed minimally; half-life was 4.5 hours in the historical control group and 4.4, 6.1, 10.6, and 14.1 hours in mild RI, moderate RI, advanced RI, and ESRD, respectively. Hemodialysis cleared approximately 30% of the dose. The recommended dose in mild to moderate RI and after hemodialysis is unchanged at 1 g daily; and in advanced RI and ESRD is reduced to 0.5 g daily. If the daily dose is given 6 hours prior to hemodialysis, a supplementary 150-mg dose (30% of the daily dose) is recommended postdialysis.
    The Journal of Clinical Pharmacology 11/2006; 46(10):1128-38. · 2.84 Impact Factor
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    ABSTRACT: The disposition of caspofungin, a parenteral antifungal drug, was investigated. Following a single, 1-h, intravenous infusion of 70 mg (200 microCi) of [(3)H]caspofungin to healthy men, plasma, urine, and feces were collected over 27 days in study A (n = 6) and plasma was collected over 26 weeks in study B (n = 7). Supportive data were obtained from a single-dose [(3)H]caspofungin tissue distribution study in rats (n = 3 animals/time point). Over 27 days in humans, 75.4% of radioactivity was recovered in urine (40.7%) and feces (34.4%). A long terminal phase (t(1/2) = 14.6 days) characterized much of the plasma drug profile of radioactivity, which remained quantifiable to 22.3 weeks. Mass balance calculations indicated that radioactivity in tissues peaked at 1.5 to 2 days at approximately 92% of the dose, and the rate of radioactivity excretion peaked at 6 to 7 days. Metabolism and excretion of caspofungin were very slow processes, and very little excretion or biotransformation occurred in the first 24 to 30 h postdose. Most of the area under the concentration-time curve of caspofungin was accounted for during this period, consistent with distribution-controlled clearance. The apparent distribution volume during this period indicated that this distribution process is uptake into tissue cells. Radioactivity was widely distributed in rats, with the highest concentrations in liver, kidney, lung, and spleen. Liver exhibited an extended uptake phase, peaking at 24 h with 35% of total dose in liver. The plasma profile of caspofungin is determined primarily by the rate of distribution of caspofungin from plasma into tissues.
    Antimicrobial Agents and Chemotherapy 04/2004; 48(3):815-23. · 4.57 Impact Factor
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    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.
    Antimicrobial Agents and Chemotherapy 03/2004; 48(2):521-4. · 4.57 Impact Factor
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    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.
    Antimicrobial Agents and Chemotherapy 11/2002; 46(11):3506-11. · 4.57 Impact Factor