Related Experiment Video
Updated: Aug 12, 2025
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Pharmacokinetic profile of acyclovir in a child receiving continuous kidney replacement therapy for acute liver
Charlotte Collignon1, Charles de Marcellus2, Mehdi Oualha2,3
1Pediatric Intensive Care Unit, APHP University Hospital Necker-Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France. charlotte.collignon@aphp.fr.
Insights
Continuous kidney replacement therapy (CKRT) can alter acyclovir pharmacokinetics in children with acute liver failure. This case study shows standard dosing achieved appropriate acyclovir exposure during CKRT, but further research on lower doses is recommended.
Area of Science:
- Pediatric Nephrology
- Pharmacokinetics
- Critical Care Medicine
Background:
- Severe acute liver failure in critically ill children can be caused by HSV infection, necessitating acyclovir treatment.
- Continuous venovenous hemodiafiltration (CVVHDF), a type of continuous kidney replacement therapy (CKRT), is used for these patients.
- CKRT may impact acyclovir pharmacokinetics due to its properties and CVVHDF settings.
Purpose of the Study:
- To describe acyclovir pharmacokinetics in a pediatric patient with acute liver failure undergoing CKRT.
- To evaluate the effectiveness of standard acyclovir dosing during CKRT.
Main Methods:
- A 21-month-old female with liver failure received intravenous acyclovir during CKRT with high flow rates.
- Plasma and effluent acyclovir concentrations were measured using liquid chromatography-tandem mass spectrometry.
- Acyclovir clearance was estimated using two methods: pre- and post-filter concentrations and dialysate flow rates.
Main Results:
- Acyclovir clearance was estimated between 19.2-26.3 mL/min (method 1) and 27.6-44.3 mL/min (method 2).
- Peak plasma acyclovir concentrations were high (28 mg/L), exceeding the therapeutic index.
- The area under the curve (AUC) indicated appropriate acyclovir exposure despite high peak concentrations.
Conclusions:
- Standard acyclovir dosing provided adequate exposure in this pediatric patient on CKRT for acute liver failure.
- Further studies are needed to investigate potentially lower acyclovir dosing regimens during CKRT.
Background:
Continuous venovenous hemodiafiltration (CVVHDF) is one of the treatments of critically ill children presenting severe acute liver failure. This affliction might be induced by HSV infection requiring a treatment by acyclovir. Continuous kidney replacement therapy (CKRT) can alter its pharmacokinetics, according to its physicochemical properties and CVVHDF settings.
Case-Diagnosis/Treatment:
The patient was a 21-month-old female presenting liver failure with hyperammonemia treated by acyclovir with presumed HSV infection. CKRT was initiated on day 1 with substantial replacement and dialysate flow rates (respectively 75 and 220 mL/kg/h). Acyclovir was intravenously administered every 8 h with a 1-h infusion of 500 mg/m2. Plasma and effluent concentrations were measured by liquid chromatography-tandem mass spectrometry assay to estimate the area under a curve (AUC) and CKRT clearance by 2 methods (one based on pre- and post-filter concentrations and the other one on dialysate flow rates). Clearance was estimated between 19.2 and 26.3 mL/min with the first method and between 27.6 and 44.3 mL/min with the second one. Concentrations were highly above the therapeutic index (peak concentration was measured at 28 mg/L), but AUC was appropriate.
Conclusions:
This case describes acyclovir pharmacokinetics during CKRT in a pediatric patient treated by acyclovir. The patient was treated with adapted exposure with the usual dosing, but lower dosing should be investigated with complementary studies.
Trial Registration:
ClinicalTrials.gov NCT02539407.
More Related Videos
07:13Digital Home-Monitoring of Patients after Kidney Transplantation: The MACCS Platform
Published on: April 12, 2021
06:14Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients
Published on: October 15, 2017
Related Concept Videos
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:22Acute Kidney Injury I: Introduction
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:30Continuous Renal Replacement Therapy
01:22Acute Kidney Injury VI: Nursing Management
01:06Renal Drug Clearance: Overview
Renal clearance can be calculated using different methods. One approach is to divide the urinary drug excretion rate by the plasma drug concentration. This method directly measures renal clearance, indicating the kidneys' efficiency in...