← Pediatric research · References

Pediatric model comparison and evidence

Abdalla 2020 and Zeng 2009 predict different exposures in different pediatric populations. The comparison evaluates typical IV concentration profiles across body weight and renal function.

Model predictions

Illustrative 10 mg/kg every 8 hours, infused over 1 hour. Renal inputs are indexed mL/min/1.73 m². Clearance is L/h; peak and trough are theoretical steady-state mg/L. These are model predictions, not patient observations. Random effects are excluded.

Zeng: CL = 3.55 × (weight/19.6)^0.75 × (CLCR/3.7)^0.51; V = 7.36 × (weight/19.6). Convert the indexed renal input to CLCR in L/h/m² by multiplying by 60/1000/1.73. All rows lie within both studies’ marginal weight and renal ranges; this does not establish joint covariate support.

Evidence base and study limitations

• Zeng L, et al. (2009) — Population pharmacokinetics of acyclovir in children and young people with malignancy after administration of intravenous acyclovir or oral valacyclovir. 43 patients; final Table 3 supports a separate pediatric IV comparison. Counahan renal estimates and L/h/m² units differ from Abdalla’s historical Schwartz input.
• Soul-Lawton J, et al. (1995) — Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of acyclovir, following oral administration to humans. Mean absolute bioavailability 54.2% in 12 healthy volunteers. AyFlux’s 54.5% default remains attributed to the product label, not this result.
• Weller S, et al. (1993) — Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Human dose-escalation evidence for less-than-dose-proportional oral exposure; does not determine a universal saturation constant.
• Kably B, et al. (2025) — Population pharmacokinetics of aciclovir and its major metabolite 9-carboxymethoxymethylguanine and safety profile of valaciclovir in early liver transplant recipients. 50 transplant recipients; only one participant had eGFR below 30. Joint model and simulations support renal-dependence research, not dialysis validation or a toxicity threshold.
• Stathoulopoulou F, et al. (2002) — Evaluation of Valaciclovir Dosage Reduction in Continuous Ambulatory Peritoneal Dialysis Patients. 12 participants after one 500 mg dose; only eight had three timed plasma samples. Apparent clearance is approximate; full AUC, bioavailability and dialysis clearance were not established.
• Stathoulopoulou F, et al. (1996) — Clinical Pharmacokinetics of Oral Acyclovir in Patients on Continuous Ambulatory Peritoneal Dialysis. Oral acyclovir in CAPD; do not transfer formulation-dependent apparent parameters directly to valacyclovir or IV dosing.
• Kacirova I, et al. (2022) — Therapeutic monitoring of serum concentrations of acyclovir and its metabolite 9-(carboxymethoxymethyl) guanine in routine clinical practice. 27 patients receiving IV acyclovir. Renal strata differed in dose and demographics; pooled troughs are observational comparators, not a controlled dose-response experiment.
• Funaki T, et al. (2015) — Therapeutic Drug Monitoring in Neonatal HSV Infection on Continuous Renal Replacement Therapy. One neonate with changing CRRT and plasma exchange. Circuit and treatment timing prevent use as a general neonatal dialysis-clearance constant.
• D’Agate S, et al. (2024) — Population pharmacokinetics and dose rationale for aciclovir in term and pre-term neonates with herpes. Final analysis: 83 samples from 28 infants. Reanalysis of earlier neonatal trial data; not an independent validation cohort for the original model.
• Sun M, et al. (2025) — Revisiting Acyclovir Dosing for Adult Viral Encephalitis Using a Full Bayesian LeiCNS PBPK Modeling Approach. CNS PBPK analysis distinguishes CSF from brain extracellular fluid. Reuses published observations; model code is available from the authors on reasonable request.
• Laskin OL, et al. (1982) — Effect of Renal Failure on the Pharmacokinetics of Acyclovir. Six anuric participants; likely overlapping with the other 1982 Laskin/Krasny reports. Potential cohort overlap limits interpretation as independent evidence.
• Krasny HC, et al. (1982) — Influence of Hemodialysis on Acyclovir Pharmacokinetics in Patients with Chronic Renal Failure. Historical dialysis experiment. The reported concentration reduction is not the fraction of the initial dose removed; comparisons require consistent sampling times and recovery denominators.

Parameter extraction and cohort overlap · Calculation methods