Initial Dosage Regimen of Vancomycin for Septic Shock Patients: A Pharmacokinetic Study and Monte Carlo Simulation
Wasan Katip Bpharm*,***, Sutep Jaruratanasirikul MD**, Sutthiporn Pattharachayakul PharmD***, Wibul Wongpoowarak MSc****, Arnurai Jitsurong MSc*****
Affiliation : * The College of Pharmacotherapy of Thailand, The Pharmacy Council of Thailand, Nonthaburi, Thailand ** Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand *** Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand **** Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand ***** Department of Toxicology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
Objective : To evaluate the pharmacokinetic parameters of vancomycin in septic shock patients and to determine the
vancomycin dosage to achieve requisite pharmacokinetic/pharmacodynamic (PK/PD) target against methicillin resistant
Staphylococcus aureus (MRSA) in patients with septic shock.
Material and Method: Pharmacokinetic parameters of vancomycin in 12 septic shock patients were assessed. Then, the
Monte Carlo simulation was performed to calculate the probabilities of target attainment (PTAs) to reach target AUC0-24/MIC
of 400 and 450 mg•h/L.
Results : The total clearance (CL) and the volume of the central compartment (Vc) of vancomycin was 3.341.39 L/h and
0.141.43 L/kg, respectively. For Staphylococcal spp. with low MICs of 0.125 and 0.5 mg/L, the administration of vancomycin
30 mg/kg as the loading dose, followed by the maintenance dose of 20 mg/kg every six, eight, 12, and 24 hours achieved
>90% PTAs to reach target AUC0-24/MIC. For pathogens with MIC of 1, and 1.5 mg/L, the vancomycin maintenance dose
of 20 mg/kg every six, eight, and 12 hours and every six and eight hours respectively to achieve >90% PTA.
Conclusion : High dose of vancomycin is required to achieve PK/PD target for treatment of MRSA septic shock, especially
if MRSA MIC is higher than 1 mg/L.
Keywords : Monte Carlo simulation, Vancomycin, septic shock, Pharmacokinetics/pharmacodynamics, Loading dose
