This is an exploratory pharmacokinetic trial in healthy volunteers (cohort A) and patients with severe burns admitted to the ICU (cohort B). The Information retrieved by these investigations will help to optimize antiinfective treatment in burn victims.
Conditions
Interventions
Product Name: Ceftriaxon
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: CEFTRIAXONE
CAS Number: 73384-59-5
Current Sponsor code: not applicable
Other descriptive
Sponsors
Clinical Pharmacology, MUV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort A: • Age: 18 – 55 years • Healthy male subjects • Good state of health (mentally and physically) • A signed and dated written informed consent form. • The subject is able to understand and willing to comply with protocol requirements and timetables, instructions and protocol-stated restrictions. • Negative serology (human immunodeficiency virus, hepatits B-AG and C-AB) at screening. • Vital signs should be within the following range: o Systoloc blood pressure, 90-140 mmHg o Diastolic blood pressure, 45-90 mmHg o Puls rate, 45-90 bpm Cohort B: As this study involves intubated and unconscious ICU patients, the study will be performed if inclusion and exclusion criteria are fulfilled. Informed consent will be sought from the patient as soon as he/she is able to comprehend the full content of the study. • Age: > 18 • Male or female • Burn victims admitted to the ICU • Patients prior or after surgical reconstruction of the affected wound areas. • Patients receiving an antimicrobial therapy (clindamycin, meropenem, vancomycin, ceftriaxone, piperacillin/tazobactam or efuroxime) or antimycotic therapy (voriconazol) • May or may not apply: Patients receiving albumin supplementation for therapeutic purposes (e.g. hypalbuminemia or hypovolemia) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 82 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: Cohort A: • Any acute or chronic illness or clinically relevant (Investigator’s judgment) abnormality identified on the screening medical assessment, laboratory tests or ECG, unless in the opinion of the Investigator it will not interfere with the study procedures, affect the outcome of the study or compromise the safety of the subject. • Use of prescription or non-prescription drugs within 7 days or 10 times the elimination half-life (whichever is longer) prior to the first dose of study medication. • Intake of grapefruit juice within 1 week prior to study day. • History of severe allergic or anaphylactic reactions to any medication • Any disease or medical condition considered relevant for proper performance of the study or risk to the patient at the discretion of the investigator Cohort B: • Known allergy or hypersensitivity against study drug or drug class • History of severe allergic or anaphylactic reactions to any medication • Any disease or medical condition considered relevant for proper performance of the study or risk to the patient at the discretion of the investigator • Any additional drug treatment and/or medical intervention (e.g. hemofiltration or hemodialysis,..) considered relevant for proper performace of the study or risk to the patient at the discretion of the investigator • History or presence of significant disease state(s) incompatible with study participation in the judgment of the investigators • Sero-positivity for human immunodeficiency virus (HIV), all patients will undergo testing prior inclusion • Sero-positivity for hepatitis B or C virus (HepB antigen, HepC antibody), all patients will undergo testing prior inclusion • Pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine bound and unbound drug concentrations vs. time profile of antiinfectives in plasma in healthy subjects (cohort A) and burn patients (cohort B). Collected pharmacokinetic (PK) data will be described as area under the concentration time curve (AUC), maximum concentration (Cmax) and half-life (t1/2). For alle participants of cohort B data mentioned above will be determined for each individual participant prior to albumin infusion. ;Secondary Objective: oTo evaluate the differences in PK of antiinfective drugs collected from healthy subjects (cohort A) and patients (cohort B; prior albumin substitution). oTo determine PK data, incl. AUC, Cmax, t1/2, elimination and clearance of total drug concentration in plasma after albumin substitution. oTo evaluate the differences in PK of antiinfective drugs before and after albumin sublimentation in plasma and microdialysis samples. oTo measure lactate/pyruvate ratios over time by means of microdialysis (applies to cohort B) ;Primary end point(s): •Area under the concentration time curve (AUC), maximum concentration (Cmax), time of maximum plasma concentration (tmax), half-life (t1/2), volume of distribution (VD), clearance (CL); •Measurement of lactate, pyruvate and lactate/pyruvate (L/P) ratio before albumin substitution (applies to cohort B only).;Timepoint(s) of evaluation of this end point: Cohort A: after administration of study medication (single dose) on the study day Cohort B: after administration of study medication after reaching steady state condition and further, if applicable, after albumin sublimentation on study days. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Pharmacokinetic (PK) data, incl. area under the concentration time curve (AUC), maximum concentration (Cmax), half-life (t1/2), • Elimination and clearance of total concentrations of antiinfectives in plasma after albumin substitution (applies to cohort B). • Evaluation of differences in PK of drug treatment before and after albumin application (applies to cohort B) in plasma and microdialysate. • Measurement of lactate/pyruvate ratio by means of microdialysis (applies to cohort B). ;Timepoint(s) of evaluation of this end point: on study days, for the whole duration of the study including follow-up of adverse events if necessary | — |
Countries
Austria
Contacts
Public ContactOffice
Clinical Pharmacology, MUV
Outcome results
None listed