Pharmacokinetics of Ertapenem in Colorectal Tissue.
Summary of "Pharmacokinetics of Ertapenem in Colorectal Tissue."
Background: There are only limited data on tissue kinetics of ertapenem in colorectal tissue more than 3 h after administration of the drug. The purpose of this study was to assess the pharmacokinetics (PK) of ertapenem in colorectal tissue via population PK modeling. Patients and Methods: Patients ≥18 years requiring surgical intervention at the colon and/or rectum were eligible (ClinicalTrials.gov identifier: NCT 00535652). Tissue and blood samples were taken during surgery after a single dose of 1 g ertapenem. Ertapenem concentration was determined by high-performance liquid chromatography/mass spectrometry. Population PK modeling was performed in S-ADAPT. Results: Twenty-three patients were enrolled. The highest tissue concentration was 6.4 ± 2.3 mg/kg, the highest total plasma concentration 51.34 ± 9.4 mg/l, the highest unbound plasma concentration 7.05 ± 1.1 mg/l, and the unbound fraction in plasma was 14-15% for total ertapenem concentrations below approximately 22 mg/l, 19% at 100 mg/l, and 25% at 250 mg/l. The estimated geometric mean terminal half-life was 2.5 h for plasma and tissue. In the Monte Carlo simulation, a single dose of 1,000 mg ertapenem achieved robust (≥90%) probabilities of target attainment up to a minimum inhibitory concentration (MIC) of approximately 2 mg/l for the bacteriostasis target (free time above MIC, fT(>)(MIC) = 20%) and up to 0.25-0.5 mg/l for the near-maximal killing target (40% fT(>)(MIC)). Conclusion: Our data indicate an adequate penetration of ertapenem into uninfected colorectal tissue up to 8.5 h (35% of the dosing interval) after administration of 1 g intravenously.
Affiliation
Department§ of Visceral Surgery, University of Ulm, Ulm, Germany.
Journal Details
This article was published in the following journal.
Name: Chemotherapy
ISSN: 1421-9794
Pages: 437-448
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22189340
- DOI: http://dx.doi.org/10.1159/000333377
Medical and Biotech [MESH] Definitions
Aberrant Crypt Foci
Clusters of colonic crypts that appear different from the surrounding mucosa when visualized after staining. They are of interest as putative precursors to colorectal adenomas and potential biomarkers for colorectal carcinoma.
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
Genes, Mcc
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with the formation of colorectal cancer (MCC stands for mutated in colorectal cancer).
Genes, Dcc
Tumor suppressor genes located in the 18q21-qter region of human chromosome 18. The absence of these genes is associated with the formation of colorectal cancer (DCC stands for deleted in colorectal cancer). The products of these genes show significant homology to neural cell adhesion molecules and other related cell surface glycoproteins.
Colorectal Neoplasms, Hereditary Nonpolyposis
A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.
PubMed Articles
Drug interaction between tacrolimus and ertapenem in renal transplantation recipients.
To show drug interactions between tacrolimus and ertapenem, we retrospectively evaluated 13 renal transplant recipients who had been treated with ertapenem for urinary tract infections during prescrip...
Ertapenem, a novel carbapenem with long-acting antimicrobial activity, is predominantly eliminated by the kidneys. Acute prolonged neurotoxicity associated with recommended doses of ertapenem in patie...
Unusual drug reaction between valproate sodium and meropenem.
Case We describe here a rare case in which valproic acid (VPA) levels were affected by ertapenem but not by meropenem even though ertapenem and meropenem are in the same carbapenem class. A 68-year-ol...
This study was conducted in order to characterize carbapenem-nonsusceptible Klebsiella pneumoniae isolates and to evaluate the impacts of recently lowered interpretative breakpoints for carbapenems fo...
SUMMARYThere is concern that widespread usage of ertapenem may promote cross-resistance to other carbapenems. To analyse the impact that adding ertapenem to our hospital formulary had on usage of othe...
Clinical Trials
Concentration of Ertapenem in Colorectal Tissue
The purpose of this study is to determine the tissue kinetics of ertapenem in colonic tissue from three hours up to six hours (25% of dosing interval) after administration of ertapenem.
Background/rationale: Ertapenem is an innovative antimicrobial agent, which is approved in the European Union for diabetic foot infections of the skin and soft tissue. Although its antimic...
Goal of study: To assess the tissular and plasma kinetics of ertapenem; To determine the optimal dosages in the patients according to norepinephrine administration: - to assess...
Ertapenem is an antibiotic that is highly bound to plasma protein (> 95%). The effects of this high protein binding on tissue distribution of antibiotics have been few evaluated yet. In t...
Ertapenem Pharmacokinetics in Patients in Continuous Ambulatory Peritoneal Dialysis
The objective of this study is to characterize the pharmacokinetic profile of ertapenem during continuous ambulatory peritoneal dialysis (CAPD).
