Acyclovir & Valacyclovir · Dialysis + Medication Timelines ✦

Residual kidney-only acyclovir clearance mL/min

With CrCl = 0 mL/min, the model sets acyclovir renal clearance and CMMG renal clearance to exactly zero. The independent metabolism and dialysis terms are not set to zero. Renal clearance per unit of CrCl is an exploratory model assumption, not a validated patient-specific estimate. [1]

Dialysis-only acyclovir clearance mL/min

The primary scenario has zero dialysis-only clearance whenever there is no active HD, CAPD, APD dwell, or CRRT treatment. Colored comparison lines can remain above zero if other scenarios with active dialysis are overlaid. [1][2]

Total acyclovir clearance (including the patient's kidneys) mL/min

Total modeled elimination = residual kidney + nonrenal/metabolic + any currently active dialysis. It normally remains above zero when dialysis is off because the body still eliminates some acyclovir.

Acyclovir mass removed specifically by dialysis mg/hour

This is zero outside active dialysis windows. Urea Kt/V is not substituted for acyclovir clearance [1][2].

Custom dialysis schedule

Enter exact treatment times from the beginning of the simulation. For example, HD from 18 to 24 hours, or CAPD from 0–24 followed by HD from 30–34. Sequential HD, CAPD, APD, and CRRT treatments are allowed; simultaneous modalities are not modeled.

Timeline preview

Enter the exact hour from the beginning of the simulation for each administration, its route and amount. Example: 1,000 mg oral valacyclovir at hour 12, followed by 250 mg IV acyclovir at hours 24 and 48. Oral and IV drugs become acyclovir in the same central and peripheral compartments; the predicted plasma, CSF and CMMG levels carry forward across doses and dialysis transitions.

Medication administration timeline

Compare modeled outcomes

Model definitions and evidence

Acyclovir (whether administered IV or generated from oral valacyclovir) is represented with a two-compartment plasma/peripheral distribution model, separate exploratory CSF effect compartments, and a formed CMMG compartment. Residual renal clearance and time-dependent dialysis clearance act on circulating drug. The model uses representative literature dialysis values as anchors, but most remaining parameters have not been estimated from patient-level data in an externally validated population PK model [1][2].

Zero residual kidney function: both the acyclovir and CMMG renal elimination terms are multiplied by CrCl and are exactly zero at CrCl 0 mL/min, including every Monte Carlo draw. Nonrenal metabolism and active dialysis clearance remain separate, and may stay positive. The plotted renal-only clearance is separate from total drug clearance. This mathematical property is not a verified estimate of all clearance pathways in an individual patient.

Medication dosing modes (v7): The repeating regimen generates no more than the selected total number of administrations, beginning at hour 0 and spaced by the chosen interval. Administrations scheduled beyond the displayed horizon are not simulated. The custom medication timeline supports a sequence of oral valacyclovir and IV acyclovir administrations at specific hours; an IV dose is a timed infusion, while oral valacyclovir enters a first-order absorption depot. The same plasma, peripheral, CSF and CMMG amounts persist across administration-route changes and dialysis modalities. Adding or changing medication routes does not reset drug concentrations. Oral and IV dose milligram strengths must not be treated as interchangeable. This is an exploratory mathematical implementation and should not be used for clinical dosing [8] [9].

Oral valacyclovir: tablets are represented with a simplified first-order oral depot followed by rapid conversion to acyclovir. The active plasma drug is acyclovir, and CMMG is formed from it. The assumed fraction of acyclovir entering circulation after valacyclovir is 0.545, anchored to the US label's healthy-volunteer 1-g study. Dose strengths are valacyclovir free-base milligrams; conversion uses the free-base molecular-weight ratio 225.21/324.34. Absorption-rate and relative bioavailability distributions are illustrative rather than fitted; the label notes less-than-dose-proportional exposure across 250–1000 mg [8]. For exploratory input, oral valacyclovir accepts up to 6,000 mg per administration; this is not a dose recommendation. For >1,000 mg, the simplified constant-bioavailability model extrapolates beyond its anchor and may overestimate exposure due to nonlinear absorption. These oral predictions must not be used to replace IV treatment for suspected VZV encephalitis [9].

HD: an illustrative dialytic clearance anchored to the mean 81.8 mL/min in a small 1982 study [1]. CAPD: the base 3.4 mL/min was measured in a small CAPD study [2]. The dependence on exchange volume and frequency in this simulator is a hypothesis, not a fitted transport model. APD: drug extraction is approximated only while dialysate is dwelling; changing dwell duration, volume, or dialytic efficiency changes a deliberately unvalidated teaching estimate. Glucose percentage: logged but has no direct numerical effect because appropriate acyclovir transport calibration is unavailable. The ISPD guidelines discuss solution concentration, exchange volume/frequency, and treatment time as relevant prescription factors [7].

Time limits: each user-entered interval is at most 24 hours; ongoing PD or CRRT is entered as successive daily intervals. No treatment overlap is allowed. Residual CrCl is an absolute clearance proxy (mL/min), not necessarily equal to indexed eGFR. The educational Monte Carlo intervals represent variation in assumed model coefficients; they are not confidence intervals for real patients.

CNS: plasma–CSF exchange and CMMG entry are a lagged partition approximation, not a physiologically based permeability model. CNS drug concentrations, viral susceptibility, and neurotoxicity markers should not be used to identify a suitable patient dose [3][4][5].

Publications & source keys

1. Laskin OL, et al. (1982). Acyclovir kinetics in end-stage renal disease. Two-compartment kinetics and HD clearance.
2. Burgess ED, Gill MJ (1990). Intraperitoneal administration of acyclovir in CAPD. Measured peritoneal clearance.
3. Helldén A, et al. (2003). Serum CMMG and acyclovir-associated neuropsychiatric symptoms. Observational threshold.
4. Lindström J, et al. (2019). CNS acyclovir, CMMG and neurological symptoms. CSF and serum observations and barrier effects.
5. US acyclovir injection labeling. VZV in-vitro IC₅₀ range and important exposure limitations.
6. Boelaert J, et al. (1987). Multiple-dose acyclovir PK in CAPD. Illustrates limitations of smaller compartment models.
7. ISPD practice recommendations (2020). 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 adult VZV treatment guidance. Illustrates separate indications for oral antivirals in localized zoster versus IV acyclovir in severe/complicated infections.

Version 7 is for exploratory model comparison and teaching. No pharmacometric fitting to raw patient data, prospective evaluation, or clinical validation has been performed. Oral valacyclovir results are exploratory, not clinically validated for VZV CNS infections.