Pharmacokinetics Study of Polymyxin B in Patients with Sepsis
OBJECTIVE To study the pharmacokinetics of polymyxin B(PB)in sepsis patients and to provide evidence for its rational clinical use.METHODS Sepsis patients were given intravenous PB,every 12 h(q12 h),4 consecutive doses.Blood sam-ples were collected before each dose and 0.5,1,2,3,6,9,12 h after the fifth dose.The plasma concentrations of PB were deter-mined by UHPLC-MS/MS method.The main pharmacokinetic parameters were calculated by non-compartment model,and a limited sampling model was established with sparse blood concentration data points.RESULTS A total of 18 patients were included.The main pharmacokinetic parameters of PB were as follows:area under the concentration-time curve for the 24 h exposure after the fifth dose(AUC0-24 h)was(63.33±30.88)mg·h·L-1,plasma concentrations prior to the fifth dose(ρ0)was(2.01±1.54)mg·L-1,post the fifth dose peak plasma concentration(ρmax)was(6.90±4.22)mg·L-1,plasma concentrations of 12 h after the fifth dose(ρ12)was(1.64±1.04)mg·L-1,average steady-state plasma concentration(ρss,av)was(2.64±1.29)mg·L-1,trough concentrations after the first,second and third doses were(3.35±2.50)(2.74±1.60)and(1.76±1.10)mg·L-1,respectively.The recommended two-point regression equation is AUC0-12 h=2.08+1.22ρ1+9.41ρ6.CONCLUSIONS There are individual variabilities in the pharmacoki-netic parameters of PB in patients with sepsis.The loading dose of the first dose can reach the steady-state concentration as soon as possi-ble,and the PB concentration point 1,6 h after administration can be used to estimate AUC0-24h.It is suggested to monitor PB-AUC0-24 h to guide the adjustment of PB dosage in adult patients with sepsis.
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