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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 samples 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 determined 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 pharmacokinetic parameters of PB in patients with sepsis. The loading dose of the first dose can reach the steady-state concentration as soon as possible, and the PB concentration point 1,6 h after administration can be used to estimate AUC0-24 h. 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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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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