LD Suite — Levodopa PK Tools

LD Suite

Levodopa Pharmacokinetic Tools

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Rytary Calculator

6-hour lookback window with time-weighted IR dosing. Calculates total effective LD with 200/210mg thresholds.

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Daily LD PK Simulator

24-hour plasma concentration curve. Scheduled doses + unlimited rescue doses with custom Rytary/IR mix.

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Equivalence Plot

Rytary vs Sinemet IR comparison. User-configurable doses with bidirectional equivalence calculation.

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Pulse Model

Three-pulse absorption window visualization. Rytary 580mg tri-phasic kinetics vs Sinemet 2×100mg.

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Peak LD

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ng/mL

Min Trough

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ng/mL

Time <810

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hrs/day

Time >2800

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hrs/day

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24-Hour Levodopa Plasma Concentration

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Rytary + rescues (total)

Rytary only (no rescues)

Equiv IR overlay

Therapeutic ≥810

High risk ≥2800

Dysk EC50 600

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\n Scheduled Doses\n ⌄\n

Morning245+145+95 default

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Noon245+145+95 default

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Evening245+145+145 default

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Bedtime245+145+95+95 default

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\n Modifiers\n ⌄\n

Show equivalent IR CD-LD overlayDashed yellow — same LD doses, IR kinetics (sharp peaks, fast drop)

High-fat breakfast with morning doseDelays Tmax +2hr, Cmax −21% (Yao et al. 2016)

High-protein meal near any doseBBB amino acid competition → ~20% CNS reduction

Poor sleep / high stressRaises effective thresholds ~120 ng/mL

PK profile

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\n Rescue / PRN Doses · added to main curve\n ⌄\n

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\n PK model: Bateman 1-compartment, unit-corrected (mg×1000/L = ng/mL). CL/F=56.8 L/hr, V/F=114.4 L, ke=0.497 hr⁻¹ (FDA NDA 203312). Rytary tri-phasic: ka_IR=3.2, ka_ER1=0.55, ka_ER2=0.18 hr⁻¹ (fractions 27/48/25%). IR CD-LD: ka=3.5 hr⁻¹. PD correction +38% Cmax. Food effect: Yao et al. 2016. EC50: Mao et al. 2013. Semi-quantitative — not a substitute for clinical judgment. Intrasubject variability ±20%.\n

Pulse 1 · IR phase (27%) · 0–2 hr

Pulse 2 · ER phase 1 (48%) · 2–4 hr

Pulse 3 · ER phase 2 (25%) · 4–6+ hr

Sinemet 2×100 mg IR

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Rytary 580 mg — Total (fasted)

Rytary 580 mg — Fed (high-fat +2hr delay, −21% Cmax)

Sinemet 2×100 mg IR (fasted)

Therapeutic ≥810 ng/mL (EC50 UPDRS)

Dyskinesia EC50 ≥600 ng/mL

Rytary 580 mg LD · PD Patient PK

Tmax (fasted)~2–2.5 hr

Tmax (high-fat meal)~4.5–5 hr (+2hr delay)

Cmax estimate (fasted)~2,680 ng/mL

Cmax (fed)~2,117 ng/mL (−21%)

Duration >50% Cmax4–5 hr

Absorption phasesIR 27% / ER1 48% / ER2 25%

Relative bioavailability vs IR~70%

Terminal t½1.9 hr

Fluctuation index1.5 (vs 3.2 for IR)

PD vs healthy Cmax+38% / AUC +44%

Intrasubject variability~19% CV (low)

Sinemet 2×100 mg IR · PD Patient PK

Tmax (fasted)~1.0 hr

Cmax (2×100 mg, est.)~2,180–3,010 ng/mL

Duration >50% Cmax~1.5 hr

Dose-norm Cmax10.9 ng/(mL·mg)

Absolute bioavailability~84%

Terminal t½1.6 hr

<10% peak by~5 hr

Fluctuation index3.2

Intrasubject variability~37% CV (higher)

Equivalence basisPeak CNS effect (not duration)

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Window	Time range	Absorption source	% of total Rytary dose	Approx IR equivalent	Your experiential observation
Pulse 1	0–2 hr	IR beads	~27% → ~157 mg LD active	~1× Sinemet 100 mg (157mg × 31% delivery ≈ 49mg IR-equiv)	Onset comparable to Sinemet — rapid initial effect
Pulse 2	2–4 hr	ER phase 1	~48% → ~279 mg LD active	~1× Sinemet 100 mg sustained (dominant plateau phase)	Sustained therapeutic effect — longest window
Pulse 3	4–6+ hr	ER phase 2	~25% → ~145 mg LD active	~½–1× Sinemet 100 mg waning (late tail, most variable)	Late coverage — most sensitive to food, GI motility, stress
Sinemet 2×100mg	0–2 hr	IR only	100% → 200 mg LD	Reference	Sharp peak, rapid decline — equivalent first 2hr window to Rytary Pulse 1+early 2

\n Model basis: Hsu et al. J Clin Pharmacol 2015 · Yao et al. Clin Neuropharmacol 2016 · Mittur et al. Clin Pharmacokinet 2017 · FDA NDA 203312 (CL/F = 56.8 L/hr, V/F = 114.4 L). PD patient correction +38% Cmax applied. EC50: Mao et al. J Clin Pharmacol 2013 (dyskinesia EC50 600 ng/mL, UPDRS EC50 810 ng/mL).

\n Pulse window model: The 2hr functional windows reflect the experiential pharmacodynamics of sequential bead-cohort gastric emptying pulses, not discrete bead-release events. Published absorption fractions (27/48/25%) are shown as shaded phase contributions to the total curve. The tartaric acid excipient in ER component 2 modulates dissolution by local intestinal pH, creating a progressive release gradient that may manifest as functionally distinct motor windows. Effect-site equilibration t½ ~24–36 min means CNS effect lags plasma by ~30 min, further blurring phase boundaries experientially.

\n Equivalence note: Dr. Yang's equivalence claim (Rytary 580mg ≈ Sinemet 2×100mg) refers to comparable peak motor effect, not total exposure or duration. Rytary sustains therapeutic concentration for ~4–5hr vs ~1.5hr for Sinemet. This is a semi-quantitative decision-support model — not a substitute for formal PK studies or clinical judgment.\n

\n \n Rytary Dose\n Total LD mg (e.g., 245, 485, 580)\n \n

\n \n mg LD\n

\n \n IR CD/LD Dose\n Total LD mg (e.g., 100, 200, 250)\n \n

\n \n mg LD\n

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Rytary → IR Equivalent

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Peak motor effect comparable to

IR → Rytary Equivalent

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Peak motor effect comparable to

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\n Rytary (single dose, fasted)\n

\n Sinemet IR (single dose, fasted)\n

\n Rytary (fed, high-fat meal)\n

\n Therapeutic window (EC50 UPDRS ~810 ng/mL threshold)\n

\n Dyskinesia risk (EC50 ~600 ng/mL lower bound shown)\n

Rytary 580 mg LD

Tmax (fasted)~2.5 hr

Tmax (fed)~4.5–5 hr

Cmax (fasted, est.)~2680 ng/mL

Duration >50% Cmax~4–5 hr

Absorption phasesIR 27% / ER1 48% / ER2 25%

Relative bioavail.~70% vs IR

t½ (terminal)1.9 hr

Sinemet 200 mg IR

Tmax (fasted)~1.0 hr

Cmax (est.)~2188 ng/mL

Duration >50% Cmax~1.5 hr

Dose-norm Cmax10.9 ng/(mL·mg)

Bioavailability~84% absolute

t½ (terminal)1.6 hr

<10% peak by~5 hr

\n Model basis: Hsu et al. (J Clin Pharmacol 2015), Yao et al. (Clin Neuropharmacol 2016), Mittur et al. (Clin Pharmacokinet 2017), FDA NDA 203312. PK model uses published CL/F = 56.8 L/hr, V/F = 114.4 L, tri-phasic Rytary absorption (Ka1 back-calculated from 27%/48%/25% fraction split and published Tmax/curve shape). IR CD-LD modeled as standard 1-compartment first-order absorption/elimination. PD patient correction factor (+38% Cmax, +44% AUC vs healthy subjects) applied to both curves.

\n Equivalence claim context: Dr. Yang's equivalence of Rytary 580 mg ≈ Sinemet 2×100 mg refers to comparable peak motor effect, not duration or total exposure. The key difference is duration: Sinemet 2×100 mg sustains therapeutic levels for ~1.5 hr; Rytary 580 mg sustains them for ~4–5 hr. This tool scales doses proportionally based on the 580:200 reference ratio (2.9:1). This is a semi-quantitative decision-support model — not a substitute for clinical judgment.\n

Daily LD PK Simulator

Rytary 580 mg · Three-Pulse Window Modelvs Sinemet 2×100 mg IR

Rytary 580 mg LD · PD Patient PK

Sinemet 2×100 mg IR · PD Patient PK

Rytary vs Sinemet IR

Rytary 580 mg LD

Sinemet 200 mg IR

Rytary 580 mg · Three-Pulse Window Model
vs Sinemet 2×100 mg IR