Population Pharmacokinetics and Monte Carlo Dosing Simulations of Meropenem During the Early Phase of Severe Sepsis and Septic Shock in Critically Ill Patients in Intensive Care Units

• Status: Completed
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective, noncomparative study to assess the pharmacodynamics of meropenem during early phase of severe sepsis and septic shock in critically ill patients in an intensive care unit.

Clinical and laboratory data such as age,sex, body weight, electrolyte, vital signs, APACHE II score, SOFA score, BUN, Cr and blood culture will be collected.

Twelve patients will be enrolled in this study. Meropenem pharmacokinetic will be carried out during the first and second dose after 1g meropenem administration. Blood samples (approximately 3 ml) will be obtained by direct venepuncture at the following time: 0, 0.25, 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 8, 8.5, 9, 9.5, 10, 12, 14 and 16 h.

Meropenem assays will be performed by modified method of Ozkan et al. (Biomed. Chromatogr., 2001).

The pharmacokinetics of meropenem will be modelled from concentration-time profile using compartmental model. Monte Carlo simulation to assess PK/PD index as 40% and 100% T>MIC will be conducted and the results will be reported as % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response)

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sutep Jaruratanasirikul
• Collaborator: Prince of Songkla University
• Treatments: Meropenem; Thienamycins

Criteria

Inclusion Criteria:

1. Patient age > 18 years

2. Patients who diagnosed as severe sepsis or septic shock, either at admission or during the ICU stay. Sepsis is the systemic response to infections defined by two or more of the following conditions: body temperature of >38 oC or <36 oC; heart rate of > 90 beats per min; respiratory rate of >20 breaths per min or a PaCO2 of <32 mmHg; or leucocyte count >12,000 cell/mm3, <4,000 cell/mm3 or 10% immature (band) forms. Severe sepsis is defined by sepsis associated with organ dysfunction, hypoperfusion, or hypotension (systolic arterial pressure <90 mmHg, mean arterial pressure <70 mmHg or a reduction of ≥40 mmHg from baseline). Septic shock is defined by severe sepsis associated with hypotension despite adequate fluid resuscitation

Exclusion Criteria:

1. Patients who are pregnant.

2. Patients who have documented hypersensitivity to carbapenems.