| Objectives: To explore the characteristics of vancomycin pharmacokinetic and establish vancomycin population pharmacokinetic model in patients with peritoneal dialysis related peritonitis(PDRP).To provide the theoretical basis for patients with PDRP in clinic.Methods: 21 patients with PDRP who administered vancomycin were collected.The collected data included demographic characteristics(such as gender,age,height,body weight),drug utilization,peritoneal dialysis time,peritoneal dialysis schedule,indicators of liver and kidneys,the Peritoneal dialysate and blood samples after different time of administered vancomycin etc.The concentrations of Peritoneal dialysate,serum total and unbound vancomycin were detected by LC-MS/MS.Data were analyzed with NONMEM.Model evaluation was based on parameter plausibility and prediction-corrected visual predictive checks.Finally the clinical dosage schedule was simulated in a standard patients with weight 70 kg and height 176 cm based on the established model.Results:(1)This study established detection method of the vancomycin concentration in Peritoneal dialysate and the unbound and total vancomycin concentration in serum.The linear range was 0.1-16 ug/ml,and the lower quantitative limit was 0.1 ug/ml for vancomycin in Peritoneal dialysate.The linear range was 0.15-30 ug/ml,and the lower quantitative limit was 0.15 ug/ml for vancomycin in serum.The intra-and inter-day precisions(RSD)were less than 10%,and the accuracy was 89%-106%.(2)The transfer parameter(Q1)between Peritoneal dialysate and serum unbound vancomycin is 0.969 L/h(0.808-1.295),the between subject variability of Q1 was 25.9%(15.6%-60%).The clearance(CL)of serum unbound vancomycin was 1.45 L/h(1.18-1.84),the between subject variability of CL was 43.6%(32.5%-54.3%).The central distribution volume(V2)of serum unbound vancomycin was 120 L(59.19-159.15),the between subject variability of V2 was 19.8%(0.2%-67.5%).The peripheral distribution volume(V3)of serum unbound vancomycin was 67.35 L(16.17-112.58).The proportional residual error was 46.9%(41.0%-55.0%)for vancomycin in Peritoneal dialysate.The proportional residual error was 19.6%(0.2%-33.5%)and the additive residual error was 1.26 mg/L(0.36-1.77)for serum unbound vancomycin.(3)The protein binding parameter(Bmax)of vancomycin in serum was 11.45(4.92-21.7),the between subject variability of Bmax was 41.0%(9%-58%).The parameter Kd was 16.35 mg/L(4.57-33.4).(4)The transfer parameter(Q1)between Peritoneal dialysate and serum total vancomycin is 1.32 L/h(0.86-2.01),the between subject variability of Q1 was 50.0%(0.5%-89.7%).The clearance(CL)of serum total vancomycin was 0.726 L/h(0.287-1.351),the between subject variability of CL was 19.5%(0.2%-62.4%).The central distribution volume(V2)of serum total vancomycin was 90.4 L(20.59-204.53),the between subject variability of V2 was 44.4%(0.5%-77.1%).The peripheral distribution volume(V3)of serum total vancomycin was275 L(72.49-1320.5),the between subject variability of V3 was 117.7%(1.3%-579.1%).The proportional residual error was 47.8%(40.2%-54.3%)for vancomycin in Peritoneal dialysate.The additive residual error was 4.71 mg/L(3.02-7.54)for serum total vancomycin.(5)The clinical dosage schedule was administered vancomycin with once a day and 2000 mg dosage for standard patients.The clinical dosage can maintain total serum concentration more than 15 mg/L after 3 days.Conclusions: This study established detection method of the vancomycin concentration in Peritoneal dialysate and the unbound and total vancomycin concentration in serum;This study established the population pharmacokinetic model of Peritoneal dialysate and serum unbound and total vancomycin with peritoneal dialysis related peritonitis patients.The result will provide theoretical basis for patients with PDRP in individualized application of vancomycin in clinic. |
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