[Pharmacokinetics of vancomycin in patients with severe acute pancreatitis and its influencing factors: analysis of 7 years data].

Objective: To observe the change of the serum trough concentration and its pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP), and to analyze the factors influencing vancomycin concentration.

Methods: A retrospective analysis was conducted. Steady-state trough concentrations of vancomycin from patients (18-80 years old) with SAP concomitantly with G infection admitted to Intensive Care Unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2010 to December 2016 were enrolled. According to the usage time of vancomycin, the patients with SAP were divided into early group (onset within 21 days), middle group (onset between 21-28 days) and late group (onset over 28 days). The gender, age, body weight, clinical diagnosis, acute physiology and chronic health evaluation II (APACHE II) score, renal function, and the pharmacokinetic parameters were recorded. Influencing factors of vancomycin was analyzed by multiple linear regression and stepwise regression.

Results: Fifty-eight patients were enrolled who contained 134 times trough concentrations of vancomycin. There were 41 patients enrolled and 61 times of trough concentrations in the early group, 24 patients enrolled and 33 times of trough concentrations in the middle group, and 28 patients enrolled and 40 times of trough concentrations in the late group. There was no significant difference in gender, age, body weight, serum creatinine, creatinine clearance (CCr), albumin, APACHE II score among the three groups. There was significantly difference in the duration from the onset time to vancomycin administration between early, middle groups and late group (days: 15.9±3.2, 23.3±2.2 vs. 35.0±6.7, both P < 0.05). The positive liquid balance in early group was lower than that of late group (mL: 1 565.2±3 132.1 vs. 3 675.1±3 411.5, P < 0.01), while it was increased in the middle group as compared with that of late group (mL: 5 078.7±3 892.4 vs. 3 675.1±3 411.5, P < 0.05). The average daily dose of vancomycin in the early, middle and late groups were (14.7±5.0), (15.0±2.8), (17.0±4.2) mg/kg, respectively, and there was no significant difference (P > 0.05). Compared with the standard concentration (15 mg/L) of vancomycin, the serum trough concentration of vancomycin was significantly reduced in SAP patients [(7.5±4.3) mg/L, P < 0.01]. Apparent volume of distribution (Vd) was (72.4±15.4) L, and clearance rate (CL) was (9.0±2.8) L/h. According to the Bayesian, the serum trough concentration of vancomycin was significantly reduced in early group and middle group compared with late group (mg/L: 5.0±2.1, 7.3±2.5 vs. 11.5±5.1, both P < 0.01), CL was significantly increased (L/h: 10.5±3.0, 8.1±1.9 vs. 7.4±1.9, both P < 0.05), and Vd was significantly increased in early group compared with late group (L: 73.7±15.5 vs. 71.0±12.6, P < 0.05). It was shown by multiple linear regression analysis that there was strong relationship between serum trough concentration and the serum creatinine, CCr, average daily dose and the starting time of vancomycin treatment (r value were 0.449, -0.318, 0.373, 0.763, respectively, all P < 0.05).

Conclusions: The serum trough concentration of vancomycin was significantly reduced in SAP patients. And the earlier usage of vancomycin, the lower of the trough concentration is. Therefore, higher dosage regimen was needed to ensure the clinical effect, and reduce the bacterial resistance.