Acyclovir pharmacokinetics across kidney function and dialysis

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Scientific sources

References

Primary literature, labeling and guidance used in AyFlux. Numbers match the simulator.

Using these references

Cite the software and the studies relevant to your analysis. Read parameter sources and model assumptions and the pediatric evidence review for what each source can support.

Bibliographic details do not imply full-text review or model validation. Individual entries identify abstract-only evidence, reconstructed cases, overlapping reports and publication versions.

Renal failure and dialysis anchors · Plasma and CSF · Pediatric and population models · CRRT studies

Numbered bibliography

  1. Laskin OL, et al. Acyclovir kinetics in end-stage renal disease. Clin Pharmacol Ther. 1982;31(5):594–601. doi:10.1038/clpt.1982.83. Two-compartment kinetics and HD clearance.
  2. Burgess ED, Gill MJ. Intraperitoneal administration of acyclovir in patients receiving continuous ambulatory peritoneal dialysis. J Clin Pharmacol. 1990;30(11):997–1000. doi:10.1002/j.1552-4604.1990.tb03585.x. Measured peritoneal clearance.
  3. Helldén A, et al. High serum concentrations of the acyclovir main metabolite 9-carboxymethoxymethylguanine in renal failure patients with acyclovir-related neuropsychiatric side effects: an observational study. Nephrol Dial Transplant. 2003;18(6):1135–1141. doi:10.1093/ndt/gfg119. Observed CMMG association, not a validated diagnostic threshold.
  4. Lindström J, et al. An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study. J Antimicrob Chemother. 2019;74(12):3565–3572. doi:10.1093/jac/dkz357. CSF and serum observations and barrier effects.
  5. US acyclovir oral labeling. VZV in-vitro IC₅₀ range and important exposure limitations.
  6. Boelaert J, et al. Multiple dose pharmacokinetics of intravenous acyclovir in patients on continuous ambulatory peritoneal dialysis. J Antimicrob Chemother. 1987;20(1):69–76. doi:10.1093/jac/20.1.69. Fitted three-compartment plasma, peripheral and peritoneal-dialysate kinetics; numerical parameters require careful model-specific matching.
  7. ISPD practice guidelines and resources. PD prescription dimensions including modality, dwell/exchange parameters and dialysate solutions.
  8. VALTREX prescribing information, clinical pharmacology. Valacyclovir is rapidly converted to acyclovir; reported mean absolute acyclovir bioavailability 54.5% ± 9.1% after 1 g oral dose; tablets labeled in valacyclovir free-base equivalents; oral exposure is not strictly dose proportional.
  9. NIH VZV guidance for adults and adolescents with HIV. Illustrates separate indications for oral antivirals in localized zoster versus IV acyclovir in severe/complicated infections.
  10. Acyclovir injection prescribing information: normal half-life, steady-state peak and trough, renal impairment.
  11. Oral acyclovir prescribing information: HSV-1, HSV-2, and VZV in-vitro IC₅₀ ranges, antiviral mechanism, and absence of a validated susceptibility-to-outcome relationship.
  12. Morelle J, et al. ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention. Perit Dial Int. 2021;41(4):352–372. doi:10.1177/0896860820982218. osmosis, small-solute transport, glucose gradient and ultrafiltration. Values used in this website's PD transport submodel are exploratory, not fit to an acyclovir APD dataset.
  13. National Kidney Foundation: Cockcroft–Gault equation and limitations. Historical CrCl estimator; accuracy varies with body composition, age and creatinine kinetics.
  14. NIH HSV adult/adolescent opportunistic infection guidelines: HSV CNS infection management and distinction between IV and oral antiviral regimens.
  15. Smith JP, et al. Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and systemic circulation after administration of high-dose valacyclovir in subjects with normal and impaired renal function. Antimicrob Agents Chemother. 2010;54(3):1146–1151. doi:10.1128/AAC.00729-09. Measured CSF/plasma AUC ratios; acyclovir ~0.25, CMMG ~0.025 in a small study.
  16. Shah GM, Winer RL, Krasny HC. Acyclovir pharmacokinetics in a patient on continuous ambulatory peritoneal dialysis. Am J Kidney Dis. 1986;7(6):507–510. doi:10.1016/S0272-6386(86)80193-7. Reported peritoneal clearance 4.4 mL/min; single-patient evidence.
  17. Lycke J, Malmström C, Ståhle L. Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir. Antimicrob Agents Chemother. 2003;47(8):2438–2441. doi:10.1128/AAC.47.8.2438-2441.2003. Measured steady-state oral valacyclovir serum and CSF acyclovir in 10 participants with MS, without documented blood–CSF barrier disruption; provides concentration-time and CSF-to-serum AUC comparisons, not direct validation of AyFlux.
  18. Pouplin T, et al. Valacyclovir for herpes simplex encephalitis. Antimicrob Agents Chemother. 2011;55(7):3624–3626. doi:10.1128/AAC.01023-10. Small observational oral-valacyclovir CNS-infection cohort with serial plasma and CSF acyclovir measurements; treatment efficacy and equivalence to IV acyclovir were not established.
  19. Helldén A, et al. The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment. J Antimicrob Chemother. 2006;57(5):945–949. doi:10.1093/jac/dkl067. Retrospective comparison of symptomatic and asymptomatic subjects; CMMG association is not proof of causation or a validated toxicity threshold.
  20. Lycke J, Andersen O, Svennerholm B, Appelgren L, Dahlöf C. Acyclovir concentrations in serum and cerebrospinal fluid at steady state. J Antimicrob Chemother. 1989;24(6):947–954. doi:10.1093/jac/24.6.947. Measurements after oral acyclovir in MS; useful for CSF kinetics context but not a direct AyFlux route benchmark (oral acyclovir is not implemented).
  21. Almond MK, Fan S, Dhillon S, Pollock AM, Raftery MJ. Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis. Nephron. 1995;69(4):428–432. doi:10.1159/000188514. Oral acyclovir concentrations and HD removal in seven oliguric patients; the studied oral-aciclovir route is not available in AyFlux.
  22. Vasquez Vasquez JA, et al. Neurotoxicity from inordinate valacyclovir dosage in an elderly woman with stage 5 chronic kidney disease. Br J Clin Pharmacol. 2025;91(8):2469–2473. doi:10.1002/bcp.70138. Published single case with blood, dialysate and urine measurements; body-burden estimates remain model-dependent. The 2024 preprint was not peer-reviewed; it is retained as publication history; the current HD reconstruction cites the final journal article. Publication does not create a second independent case or validate AyFlux.
  23. Sadjadi S-A, Regmi S, Chau T. Acyclovir neurotoxicity in a peritoneal dialysis patient: report of a case and review of the pharmacokinetics of acyclovir. Am J Case Rep. 2018;19:1459–1462. doi:10.12659/AJCR.911520. PD-to-HD clinical case, not prospective dose-response validation or a neurotoxicity cutoff.
  24. Bodilsen J, Nielsen H, Whitley RJ. Valaciclovir therapy for herpes encephalitis: caution advised. J Antimicrob Chemother. 2019;74(6):1467–1468. doi:10.1093/jac/dky568. Clinical commentary cautioning against inferring HSV encephalitis treatment efficacy from CSF concentrations or in-vitro inhibitory concentrations; not an independent PK validation cohort.
  25. Abdalla S et al. Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens. Antimicrob Agents Chemother. 2020;64:e01426-20. doi:10.1128/AAC.01426-20. Source for the separate pediatric IV research module; not validation of the adult engine or pediatric dialysis.
  26. Zeng L, et al. Population pharmacokinetics of acyclovir in children and young people with malignancy after administration of intravenous acyclovir or oral valacyclovir. Antimicrob Agents Chemother. 2009;53(7):2918–2927. doi:10.1128/AAC.01138-08. 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.
  27. Soul-Lawton J, et al. Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of acyclovir, following oral administration to humans. Antimicrob Agents Chemother. 1995;39(12):2759–2764. doi:10.1128/aac.39.12.2759. Mean absolute bioavailability 54.2% in 12 healthy volunteers. AyFlux’s 54.5% default remains attributed to the product label, not this result.
  28. Weller S, et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993;54(6):595–605. doi:10.1038/clpt.1993.196. Human dose-escalation evidence for less-than-dose-proportional oral exposure; does not determine a universal saturation constant.
  29. Kably B, et al. Population pharmacokinetics of aciclovir and its major metabolite 9-carboxymethoxymethylguanine and safety profile of valaciclovir in early liver transplant recipients. J Antimicrob Chemother. 2025;80(5):1302–1308. doi:10.1093/jac/dkaf070. 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.
  30. Stathoulopoulou F, et al. Evaluation of Valaciclovir Dosage Reduction in Continuous Ambulatory Peritoneal Dialysis Patients. Nephron. 2002;91(1):164–166. doi:10.1159/000057621. 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.
  31. Stathoulopoulou F, et al. Clinical Pharmacokinetics of Oral Acyclovir in Patients on Continuous Ambulatory Peritoneal Dialysis. Nephron. 1996;74(2):337–341. doi:10.1159/000189332. Oral acyclovir in CAPD; do not transfer formulation-dependent apparent parameters directly to valacyclovir or IV dosing.
  32. Kacirova I, et al. Therapeutic monitoring of serum concentrations of acyclovir and its metabolite 9-(carboxymethoxymethyl) guanine in routine clinical practice. Biomed Pharmacother. 2022;156:113852. doi:10.1016/j.biopha.2022.113852. 27 patients receiving IV acyclovir. Renal strata differed in dose and demographics; pooled troughs are observational comparators, not a controlled dose-response experiment.
  33. Funaki T, et al. Therapeutic Drug Monitoring in Neonatal HSV Infection on Continuous Renal Replacement Therapy. Pediatrics. 2015;136(1):e270–e274. doi:10.1542/peds.2014-3380. One neonate with changing CRRT and plasma exchange. Circuit and treatment timing prevent use as a general neonatal dialysis-clearance constant.
  34. D’Agate S, et al. Population pharmacokinetics and dose rationale for aciclovir in term and pre-term neonates with herpes. Pharmacol Res Perspect. 2024;12(3):e1193. doi:10.1002/prp2.1193. Final analysis: 83 samples from 28 infants. Reanalysis of earlier neonatal trial data; not an independent validation cohort for the original model.
  35. Sun M, et al. Revisiting Acyclovir Dosing for Adult Viral Encephalitis Using a Full Bayesian LeiCNS PBPK Modeling Approach. Clin Pharmacokinet. 2025;64(9):1413–1423. doi:10.1007/s40262-025-01545-w. CNS PBPK analysis distinguishes CSF from brain extracellular fluid. Reuses published observations; model code is available on reasonable request, not supplied in this PDF.
  36. Laskin OL, et al. Effect of Renal Failure on the Pharmacokinetics of Acyclovir. Am J Med. 1982;73(1A):197–201. doi:10.1016/0002-9343(82)90090-0. Six anuric participants; likely overlapping with the other 1982 Laskin/Krasny reports. Treat as potentially shared evidence, not three independent cohorts.
  37. Krasny HC, et al. Influence of Hemodialysis on Acyclovir Pharmacokinetics in Patients with Chronic Renal Failure. Am J Med. 1982;73(1A):202–204. doi:10.1016/0002-9343(82)90091-2. Historical dialysis experiment. The reported concentration reduction is not the fraction of the initial dose removed; match timing and the amount denominator before comparison.
  38. Boulieu R, Bastien O, Gaillard S, Flamens C. Pharmacokinetics of acyclovir in patients undergoing continuous venovenous hemodialysis. Ther Drug Monit. 1997;19(6):701–704. doi:10.1097/00007691-199712000-00016. Three adult ICU patients on CVVHD; half-life, ultrafiltrate clearance and sieving coefficient. Abstract-level values; full text not reviewed.
  39. Bleyzac N, Barou P, Massenavette B, et al. Assessment of acyclovir intraindividual pharmacokinetic variability during continuous hemofiltration, continuous hemodiafiltration, and continuous hemodialysis. Ther Drug Monit. 1999;21(5):520–525. doi:10.1097/00007691-199910000-00005. One pediatric patient; Bayesian estimates from routine monitoring. Abstract-level, qualitative.
  40. Collignon C, de Marcellus C, Oualha M, et al. Pharmacokinetic profile of acyclovir in a child receiving continuous kidney replacement therapy for acute liver failure. Pediatr Nephrol. 2023;38(10):3493–3497. doi:10.1007/s00467-023-05881-6. Single 21-month-old on CVVHDF; open access.
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