Pharmacokinetics of Intraperitoneal Vancomycin and Amikacin in Automated Peritoneal Dialysis Patients With Peritonitis.

Objective: The study aimed to evaluate the vancomycin and amikacin concentrations in serum and dialysate for automatic peritoneal dialysis (APD) patients. Methods: A total of 558 serum and dialysate samples of 12 episodes of gram-positive and 18 episodes of gram-negative peritonitis were included to investigate the relationship between vancomycin and amikacin concentrations in serum and dialysate on the first and third days of treatment. Samples were analysed 30, 120 min, and 48 h after intraperitoneal administration of vancomycin in peritonitis caused by gram-positive agents and 30, 120 min, and 24 h after intraperitoneal administration of amikacin in peritonitis caused by gram-negative agents. Vancomycin was administered every 72 h and amikacin once a day. The target therapeutic concentration of amikacin was 25-35 mg/l at the peak moment and 4-8 mg/l at the trough moment; and after 48 h for vancomycin, 15-20 mg/l at the trough moment. Results: For peritonitis caused by gram-negative agents, at the peak moment, therapeutic levels of amikacin were reached in dialysate in 80.7% of patients with evolution to cure and in 50% of patients evaluated as non-cure (p = 0.05). At the trough moment, only 38% were in therapeutic concentrations in the dialysate in the cure group and 42.8% in the non-cure group (p = 1). Peak plasma concentrations were subtherapeutic in 98.4% of the samples in the cure group and in 100% of the non-cure group. At the trough moment, therapeutic concentrations were present in 74.4% of the cure group and 71.4% of the non-cure group (p = 1). Regarding vancomycin and among gram-positive agents, therapeutic levels were reached at the peak moment in 94% of the cure group and 6% of the non-cure group (p = 0.007). After 48 h, 56.8% of the cure group had a therapeutic serum concentration whereas for the non-cure group it was only 33.3% (p = 0.39). Conclusion: Despite a small sample size, we demonstrated peak dialysate amikacin level and peak serum vancomycin level correlates well with Gram-negative and Gram positve peritonitis cure, respectively. It is suggested to study the antibiotics pharmacodynamics for a better understanding of therapeutic success in a larger sample.

Vancomycin Removal During High-Volume Peritoneal Dialysis in Acute Kidney Injury Patients.

Studies on vancomycin pharmacokinetics in acute kidney injury (AKI) patients on high-volume peritoneal dialysis (HVPD) are lacking. We studied the pharmacokinetics of intravenous (IV) vancomycin in AKI patients treated by HVPD who received a prescribed single IV dose of vancomycin (15 - 20 mg/kg total body weight) to determine the extent of vancomycin removal and to establish vancomycin dosing guidelines for the empirical treatment of AKI patients receiving HVPD. The application of 18 mg/kg vancomycin every 48 - 72 hours in AKI patients undergoing HVPD was required to maintain therapeutic concentrations.

Vancomycin Removal During High-Volume Peritoneal Dialysis in Acute Kidney Injury Patients: A Prospective Cohort Clinical Study.

INTRODUCTION: Vancomycin pharmacokinetic data in patients with acute kidney injury (AKI) on high-volume peritoneal dialysis (HVPD) are lacking. The aims were to study the pharmacokinetics of i.v. vancomycin in patients with AKI treated by HVPD who received an i.v. dose of vancomycin (15-20 mg/kg), to determine the vancomycin removal, and to establish vancomycin dosing and evaluation pharmacokinetics target attainment achievement for the empirical treatment of patients with AKI treated by HVPD. METHODS: Vancomycin was administered 1 hour before dialysis start. Samples of all dialysate were collected for a 24-hour period. Blood samples were collected after 1, 2, 4, and 24 hours of therapy. Vancomycin concentrations were determined using a liquid chromatographic (high-performance liquid chromatography)-fluorescence method. Pharmacokinetic calculations were completed assuming a 1-compartment model. RESULTS: Ten patients completed the study. The mean vancomycin dose administered was 18.0 ± 2.95 mg/kg (14.7-21.8 mg/kg) on the day of study (first day) and the mean percentage of vancomycin removal by HVPD was 21.7% ± 2.2% (16%-29%). Peritoneal clearance was 8.1 ± 2.2 ml/min (5.3-12 ml/min). The serum vancomycin half-life was 71.2 ± 24.7 hours (42-110 hours) during HVPD session, the maximum serum concentration was 26.2 ± 3.5 mg/l, which occurred 1 hour after vancomycin administration and HVPD start. Area under the curve (AUC)0-24/minimum inhibitory concentration (MIC) ratio ≥400 was achieved in all patients when MIC = 1 mg/l was considered. CONCLUSION: HVPD removes considerable amounts of vancomycin in septic patients with AKI. Administration of 18 mg/kg vancomycin each 48 to 72 hours in patients with AKI undergoing HVPD was required to reach and maintain therapeutic concentrations.

Role of Pharmacogenomics in Kidney Disease and Injury.

There has been considerable excitement in the kidney community surrounding the research findings on the genetic contributions to kidney diseases. However, positive outcomes of personalized therapeutic interventions can be circumvented by unpredictable pharmacokinetics of prescribed drugs. Furthermore, unpredictable drug disposition can result in toxicities such as kidney injury. Patient covariates, disease covariates, and pharmacogenetics all contribute to variability in drug disposition. Further treatment personalization and avoidance of drug- and biologic- induced kidney injury will require extensive knowledge and expertise in renal clinical pharmacology. The current review will focus on the pharmacogenetics of drugs and biologics used in the treatment of glomerular kidney diseases and drugs implicated in inducing kidney injury phenotypes.