Ignite Creation Date:
2024-05-05 @ 4:38 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00280514
Status:
COMPLETED
Last Update Posted:
2010-08-04
First Post:
2006-01-20
Brief Title:
Plasma and Abscess Fluid Pharmacokinetics of Cefpirome and Moxifloxacin After Single and Multiple Dose Administration
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
Plasma and Abscess Fluid Pharmacokinetics of Cefpirome and Moxifloxacin After Single and Multiple Dose Administration
Status:
COMPLETED
Status Verified Date:
2005-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Penetration of cefpirome and moxifloaxacin into abscess fluid of humans will be tested Patients with an abscess scheduled for drainage will receive study drugs single or multiple dose pus samples and plasma samples will be collected and analyzed by High pressure liquid chromatography HPLC Pharmacokinetics of the study drugs in pus and plasma will be determined using a pharmacokinetic model
Detailed Description:
Title Plasma and abscess fluid pharmacokinetics of cefpirome and moxifloxacin single dose and multiple dose administration
Background Extensive research in the field of abscess treatment has established a claim for invasive drainage as the most efficient means of resolving suppurative lesions In particular computer tomography-guided percutaneous abscess drainage has repeatedly been reported to be advantageous compared to other invasive methods However application of the percutaneous interventional method is subject to some limitations Coagulation abnormalities are considered a contraindication and the absence of a safe anatomic access route the presence of fistulas severe inflammation of organs or patients with advanced age have likewise been linked to low success rates of percutaneous abscess drainage From these considerations it becomes evident that percutaneous and surgical abscess drainage alone are not satisfactory in a number of patients suffering from abscessinfected cyst-related disease In some patients antibiotic therapy is administered in bridging them to more stable conditions that drainage can be performed Therefore it is eminent for the overall outcome of patients to select an appropriate antibiotic For this purpose a model was recently developed to simulate the concentration time-curve of fosfomycin in abscess fluid after a single dose and after multiple doses
Cefpirome and moxifloxacin are drugs which may be used in the empiric therapy of purulent infections They may be used as monotherapy or they may be combined eg with fosfomycin Cefpirome is a 4th class cephalosporin with a broad spectrum gram positive and gram negative pathogens penetrating well into soft tissues Moxifloxacin is a new fluoroquinolone with a considerable antimicrobial spectrum also penetrating excellently into soft tissues Based on the experiences with the methods and results obtained from our recent study on fosfomycin penetration into abscess fluid the present pilot study will be set out to gain PK information on the penetration properties of cefpirome and moxifloxacin into abscess fluid and abdominal cysts
Aim of the study To determine pharmacokinetics of cefpirome and moxifloxacin in abscess cyst fluid and plasma after single and multiple doses
Study design Pharmacokinetic pilot study Drug concentrations will be determined in abscess liquid upon drainage and in plasma over a period of eight hours
Study population 20 Patients with an abscess or an abdominal cyst scheduled for surgical or computer tomography-guided drainage
Methods 1 High pressure liquid chromatography 2 Analysis of computer tomography CT images 3 Pharmacokinetic simulation model
Study drugs Cefpirome Cefrom Aventis will be administered to patients intravenously as single or multiple doses of 2 g dissolved in 100 mL of distilled water over 20 minutes Moxifloxacin Avelox Bayer will be administered to patients per os as tablet as single or multiple doses of 400 mg
Patients A total of 20 patients will be enrolled in the study They will be assigned to 2 groups Group 1 single dose n 12 Group 2 multiple doses n 8
Main outcome variable The cefpirome and moxifloxacin concentrations in abscess fluid will be measured Considering plasma PK and the ratio of the surface to volume ratio of the abscess the individual concentration-versus-time curve in abscess cyst fluid will be calculated Individual pharmacokinetic parameters will be determined for abscess cyst fluid after a single dose and at steady state AUC AUC0-1224h Cmax Tmax t12ß Cavss
Additional outcome variables Plasma single dose and steady state AUC AUC0-1224h Cmax Tmax t12ß Cavss Pus and plasma ratios of AUC and Cavss to MIC TMIC The following parameters will be determined if possible the diameter of the pericapsular space with enrichment of contrast agent the degree of contrast agent enhancement in this zone and the pus density rate of drug degradation in pus at body temperature in vitro pH-value of pus pus viscosity and specific weight
Inconveniences and risks for patients
The following side effects may occur after administration of cefpirome Hypersensitivity reaction allergic skin reactions exanthema urticaria pruritus drug fever anaphylactic reactions anaphylactic shock interstitial nephritis nausea vomiting abdominal pain diarrhoea pseudomembraneous colitis elevation of liver enzymes and serum creatinine thrombocytopenia eosinophilia hemolytic anemia granulocytopenia agranulocytosis local irritation and pain at the site of injection dysgeusia
The following side effects may occur after administration of moxifloxacin
Often or occasionally Nausea diarrhea vomits dyspepsia QT-prolongation elevation of AST ALT bilirubin gamma GT amylase leucocytopenia decrease of prothrombin eosinophilia thrombocythemia thrombocytopenia anemia abdominal and head pain dizziness dysgeusia unfrequent asthenia candidosis thoracal and back pain discomfort leg pain anaphylactic reactions anaphylactic shock insomnia vortex nervousness tremor paresthesia discomposure depression hallucination depersonalization ataxia xerostomia flatulence obstipation anorexia stomatitis glossitis tachycardia edema hypertension palpitations QT-prolongation syncope atrial fibrillation angina pectoris vasodilatation hypotension ventricular arrhythmia torsade de pointe hyperglycemia hyperlipidemia elevation of prothromin icterus arthralgia myalgia tendonitis rash pruritus perspiration urticaria xerodermia amblyopia tinnitus vaginitis hepatitis ataxia tendon rupture hypernatremia hypercalcemia neutropenia hemolysis transient loss of vision
Total blood loss will be limited to a maximum of 85 mL which is usually well tolerated by patients
Riskbenefit assessment CT and abscess drainage represent standard diagnosis and therapeutic procedures Therefore any risk associated with CT or abscess drainage is not ascribed to study procedures Single and multiple doses of cefpirome maximum of 14 doses and moxifloxacin maximum of 7 doses are normally well tolerated and have very few side effects
Ongoing therapy will not be affected or changed by study procedures In summary the risk conferred to patients by study procedures appears minimal
Background Extensive research in the field of abscess treatment has established a claim for invasive drainage as the most efficient means of resolving suppurative lesions In particular computer tomography-guided percutaneous abscess drainage has repeatedly been reported to be advantageous compared to other invasive methods However application of the percutaneous interventional method is subject to some limitations Coagulation abnormalities are considered a contraindication and the absence of a safe anatomic access route the presence of fistulas severe inflammation of organs or patients with advanced age have likewise been linked to low success rates of percutaneous abscess drainage From these considerations it becomes evident that percutaneous and surgical abscess drainage alone are not satisfactory in a number of patients suffering from abscessinfected cyst-related disease In some patients antibiotic therapy is administered in bridging them to more stable conditions that drainage can be performed Therefore it is eminent for the overall outcome of patients to select an appropriate antibiotic For this purpose a model was recently developed to simulate the concentration time-curve of fosfomycin in abscess fluid after a single dose and after multiple doses
Cefpirome and moxifloxacin are drugs which may be used in the empiric therapy of purulent infections They may be used as monotherapy or they may be combined eg with fosfomycin Cefpirome is a 4th class cephalosporin with a broad spectrum gram positive and gram negative pathogens penetrating well into soft tissues Moxifloxacin is a new fluoroquinolone with a considerable antimicrobial spectrum also penetrating excellently into soft tissues Based on the experiences with the methods and results obtained from our recent study on fosfomycin penetration into abscess fluid the present pilot study will be set out to gain PK information on the penetration properties of cefpirome and moxifloxacin into abscess fluid and abdominal cysts
Aim of the study To determine pharmacokinetics of cefpirome and moxifloxacin in abscess cyst fluid and plasma after single and multiple doses
Study design Pharmacokinetic pilot study Drug concentrations will be determined in abscess liquid upon drainage and in plasma over a period of eight hours
Study population 20 Patients with an abscess or an abdominal cyst scheduled for surgical or computer tomography-guided drainage
Methods 1 High pressure liquid chromatography 2 Analysis of computer tomography CT images 3 Pharmacokinetic simulation model
Study drugs Cefpirome Cefrom Aventis will be administered to patients intravenously as single or multiple doses of 2 g dissolved in 100 mL of distilled water over 20 minutes Moxifloxacin Avelox Bayer will be administered to patients per os as tablet as single or multiple doses of 400 mg
Patients A total of 20 patients will be enrolled in the study They will be assigned to 2 groups Group 1 single dose n 12 Group 2 multiple doses n 8
Main outcome variable The cefpirome and moxifloxacin concentrations in abscess fluid will be measured Considering plasma PK and the ratio of the surface to volume ratio of the abscess the individual concentration-versus-time curve in abscess cyst fluid will be calculated Individual pharmacokinetic parameters will be determined for abscess cyst fluid after a single dose and at steady state AUC AUC0-1224h Cmax Tmax t12ß Cavss
Additional outcome variables Plasma single dose and steady state AUC AUC0-1224h Cmax Tmax t12ß Cavss Pus and plasma ratios of AUC and Cavss to MIC TMIC The following parameters will be determined if possible the diameter of the pericapsular space with enrichment of contrast agent the degree of contrast agent enhancement in this zone and the pus density rate of drug degradation in pus at body temperature in vitro pH-value of pus pus viscosity and specific weight
Inconveniences and risks for patients
The following side effects may occur after administration of cefpirome Hypersensitivity reaction allergic skin reactions exanthema urticaria pruritus drug fever anaphylactic reactions anaphylactic shock interstitial nephritis nausea vomiting abdominal pain diarrhoea pseudomembraneous colitis elevation of liver enzymes and serum creatinine thrombocytopenia eosinophilia hemolytic anemia granulocytopenia agranulocytosis local irritation and pain at the site of injection dysgeusia
The following side effects may occur after administration of moxifloxacin
Often or occasionally Nausea diarrhea vomits dyspepsia QT-prolongation elevation of AST ALT bilirubin gamma GT amylase leucocytopenia decrease of prothrombin eosinophilia thrombocythemia thrombocytopenia anemia abdominal and head pain dizziness dysgeusia unfrequent asthenia candidosis thoracal and back pain discomfort leg pain anaphylactic reactions anaphylactic shock insomnia vortex nervousness tremor paresthesia discomposure depression hallucination depersonalization ataxia xerostomia flatulence obstipation anorexia stomatitis glossitis tachycardia edema hypertension palpitations QT-prolongation syncope atrial fibrillation angina pectoris vasodilatation hypotension ventricular arrhythmia torsade de pointe hyperglycemia hyperlipidemia elevation of prothromin icterus arthralgia myalgia tendonitis rash pruritus perspiration urticaria xerodermia amblyopia tinnitus vaginitis hepatitis ataxia tendon rupture hypernatremia hypercalcemia neutropenia hemolysis transient loss of vision
Total blood loss will be limited to a maximum of 85 mL which is usually well tolerated by patients
Riskbenefit assessment CT and abscess drainage represent standard diagnosis and therapeutic procedures Therefore any risk associated with CT or abscess drainage is not ascribed to study procedures Single and multiple doses of cefpirome maximum of 14 doses and moxifloxacin maximum of 7 doses are normally well tolerated and have very few side effects
Ongoing therapy will not be affected or changed by study procedures In summary the risk conferred to patients by study procedures appears minimal
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EUdraCT no 2005-004455-35 | None | None | None |