Determination of imipenem (N-formimidoyl thienamycin) in human plasma and urine by high-performance liquid chromatography, comparison with microbiological methodology and stability

Gravallese, D A; Musson, Donald G.; Pauliukonis, L.T.; Bayne, W.F.

doi:10.1016/0378-4347(84)80069-9

Cited by 56 publications

(34 citation statements)

References 9 publications

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“…Imipenem concentrations in plasma and dialysate/ultrafiltrate were determined using reversed-phase high-performance liquid chromatography (HPLC) with UV detection according to previously published methods with minor adaptations (13,38). The HPLC system utilized a Novapak C 18 4.6-mm by 150-mm column with a guard column containing Novapak C 18 inserts (Waters, Milford, MA), and the detector was set at a wavelength of 298 nm.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

Fish

Teitelbaum

Abraham

2005

Antimicrob Agents Chemother

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The pharmacokinetics of imipenem were studied in adult intensive care unit (ICU) patients during continuous venovenous hemofiltration (CVVH; n ‫؍‬ 6 patients) or hemodiafiltration (CVVHDF; n ‫؍‬ 6 patients). Patients (mean ؎ standard deviation age, 50.9 ؎ 15.9 years; weight, 98.5 ؎ 15.9 kg) received imipenem at 0.5 g every 8 to 12 h (total daily doses of 1 to 1.5 g/day) by intravenous infusion over 30 min. Pre-and postmembrane blood (plasma) and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, and 8 or 12 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL S ) and elimination half-life (t 1/2 ) of imipenem were 145 ؎ 18 ml/min and 2.7 ؎ 1.3 h during CVVH versus 178 ؎ 18 ml/min and 2.6 ؎ 1.6 h during CVVHDF, respectively. Imipenem clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 25% and 32% of CL S , respectively. The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported. Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC up to 2 g/ml) during CVVH or CVVHDF, but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs (MIC ‫؍‬ 4 to 8 g/ml). Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients.

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

Fish

Teitelbaum

Abraham

2005

Antimicrob Agents Chemother

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“…Blood samples were collected at 0, 10,20,30,40, and 50 min and 1, 1.16, 1.33, 1.5, 2, 2.5, 3, 3.5, 4, 4. 5,6,8,12,14, and 16 h after ciprofloxacin administration. A diluted heparin solution (33 U/ml) was used to maintain the patency of the needle, and at least 1 to 1.5 ml of blood was discarded before blood was collected.…”

mentioning

confidence: 99%

“…Blood samples, which were collected in Vacutainer tubes with no anticoagulant for the determination of SBA, were allowed to clot at room temperature for 20 min and were then centrifuged (1,000 x g, 20 min, 10°C) to obtain serum. For imipenem, plasma was diluted with an equal volume of a stabilizing solution of MES (4-morpholineethanesulfonic acid) buffer and ethylene glycol (1:1), as recommended by Gravallese et al (8). This stabilization procedure was essential, because imipenem undergoes rapid inactivation under conventional conditions of sample storage.…”

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confidence: 99%

“…Urine was collected immediately before antibiotic administration and at intervals of 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 (8). Plasma (7 ml), serum (10 ml), and urine (10 ml) samples were placed in polypropylene tubes and were promptly frozen at -80'C until analysis.…”

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confidence: 99%

“…Serum inhibitory activity and SBA determinations were performed at 1,6,8, and 12 h after the beginning of drug administration in order to assess the peak and trough levels of these antibiotics. All samples were serially diluted in twofold steps from 1:2 the variance.…”

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confidence: 99%

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Comparative study of pharmacokinetics and serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin

Paradis

Vallée

Allard

et al. 1992

Antimicrob Agents Chemother

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We compared the pharmacokinetics and the serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin. Fifteen healthy volunteers received 1 g of cefpirome, ceftazidime, and ceftriaxone intravenously, 500 mg of imipenem-cilastatin intravenously, and 500 mg of ciprofloxacin orally. High-performance liquid chromatographic assays were used to quantitate unchanged antibiotic in plasma and urine. Serum bactericidal activities were determined against six clinical isolates each of Staphylococcus aureus, Enterobacter cloacae, and Pseudomonas aeruginosa by using a modified microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977). Overall, cefpirome exhibited pharmacokinetics similar to those of ceftazidime: half-life (t,/2), 1.95 h; concentration at 1 h (Clh), 47 to 49 ig/ml for both antibiotics. Ceftriaxone displayed the longest tV2 (7.65 h) and the highest Clh (137.8 iLg/ml), while we observed the shortest t1/2 (1.05 h) and the lowest Clh (19.85 Fg/ml) with imipenem. At

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Imipenem/Cilastatin for the Treatment of Infections in Hospitalized Children

Alpert¹

1985

Arch Pediatr Adolesc Med

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Determination of imipenem (N-formimidoyl thienamycin) in human plasma and urine by high-performance liquid chromatography, comparison with microbiological methodology and stability

Cited by 56 publications

References 9 publications

Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

Comparative study of pharmacokinetics and serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin

Imipenem/Cilastatin for the Treatment of Infections in Hospitalized Children

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