PK Methodology: How Our Calculator Works

Open Calculator PK Basics Guide Dosing Scenarios Reconstitution Calculator Titration Calculator

Key Takeaways

Model type: One-compartment pharmacokinetic model with first-order absorption (the Bateman equation)
Data sources: All drug parameters come from published Phase 2/3 clinical trial data and FDA prescribing information
Multi-dose handling: Superposition calculates how weekly doses accumulate and when steady state is reached
Three compounds: Retatrutide (6-day half-life), semaglutide (7-day), and tirzepatide (5-day), each with individually sourced parameters
Transparency: Every parameter is cited with its source. No proprietary or estimated values.

How the Calculator Works

GLP3Planner uses a one-compartment pharmacokinetic model with first-order absorption (the Bateman equation) to calculate drug levels over time. Drug parameters like half-life, bioavailability, and volume of distribution are sourced from published Phase 2/3 clinical trial data. For multi-dose schedules, the model uses superposition to calculate how levels accumulate and when steady state is reached.

Why Methodology Matters

Most GLP-1 "calculators" online are simple reconstitution tools that tell you how many units to draw on a syringe. That is basic arithmetic — mg ÷ concentration × 100 — which we document in full in the reconstitution math section below, alongside the standard titration ladders. But GLP3Planner also models what happens after the injection.

GLP3Planner does something different. It models what happens after the injection: how the drug absorbs into your bloodstream, how levels accumulate with repeated weekly doses, when you reach steady state, and how your levels change if you adjust your dose or skip a week. That requires pharmacokinetic modeling grounded in clinical data.

This page explains exactly how that model works, what data it uses, and where the data comes from. No black box. If you want to verify the parameters or understand the assumptions, everything is documented here with links to the original sources.

How This Compares to Other Calculators

There are several GLP-1 tools available online. Most fall into one of two categories, and GLP3Planner is designed to fill the gap between them.

Feature	Reconstitution Calculators	Simple Plotters	GLP3Planner
Syringe unit calculation	Yes	Sometimes	Yes
Drug level visualization	No	Basic decay curve	Full PK model with Bateman equation
Multi-tier titration	No	Limited	Unlimited tiers with automatic accumulation
Steady-state detection	No	No	Yes, with week-level precision
Split-dosing / microdose support	No	Rarely	Yes, any frequency
Cited clinical data sources	Rarely	Sometimes	Yes, all parameters cited

The key difference is that GLP3Planner models the full pharmacokinetic picture: absorption, accumulation, steady state, and elimination. Most other tools either stop at reconstitution math or show a single-dose decay curve without accounting for how weekly doses build up over time.

The Pharmacokinetic Model

One-Compartment Model with First-Order Absorption

GLP3Planner uses a one-compartment pharmacokinetic model. This treats the body as a single well-mixed compartment. After a subcutaneous injection, the drug:

Absorbs from the injection site into the bloodstream at a rate governed by the absorption rate constant (k_a)
Distributes throughout the body's volume of distribution (V_d)
Eliminates at a rate governed by the elimination rate constant (k_e), which is derived from the drug's half-life

In plain language: the drug enters your bloodstream from the injection site, spreads throughout your body, and your body gradually removes it. The speed of removal is determined by the half-life. For GLP-1 medications, these half-lives are long (5-7 days), which is why once-weekly dosing works and why the drug accumulates with repeated doses.^[1][2][3]

The Bateman Equation

For subcutaneous injection, drug concentration at time t after a dose is calculated using the Bateman function:

C(t) = (F * D * k_a) / (V_d * (k_a - k_e)) * (e^-k_e*t - e^-k_a*t)

C(t) = plasma concentration at time t

F = bioavailability (fraction absorbed into bloodstream)

D = dose administered (mg)

k_a = absorption rate constant (per hour)

k_e = elimination rate constant = 0.693 / (half-life in hours)

V_d = volume of distribution (liters)

This equation produces the characteristic PK curve: levels rise as the drug absorbs, peak when absorption and elimination rates are equal, then decline as elimination dominates. The shape of this curve is determined entirely by the drug's specific parameters, which is why each compound produces a slightly different profile.

Simple Mode: Exponential Decay

By default, the calculator uses a simplified model based on half-life decay:

Amount(t) = Dose * 0.5^{(t / half-life)}

This approach skips the absorption phase and models pure elimination. For weekly dosing schedules where the primary question is "what are my trough and peak levels?", this provides accurate results with faster computation. The full Bateman model is available when you need to see the absorption curve or model non-standard injection intervals.

How to Read Your PK Chart

The interactive chart produced by the calculator shows your modeled drug levels over time. Here is what each part of the chart tells you:

GLP3Planner calculator showing an interactive pharmacokinetic chart with dose markers and drug level curve

The GLP3Planner calculator showing a multi-tier dosing schedule with accumulation and steady state.

The Curve

The main line shows total drug amount in your body over time. It rises with each injection and gradually declines as the drug is eliminated. Over weeks of consistent dosing, the baseline rises as the drug accumulates.

Peaks

The highest points on the curve, occurring shortly after each injection. At steady state, peaks become consistent from dose to dose. Higher peaks correlate with stronger effects and potentially more side effects.

Troughs

The lowest points, occurring just before the next injection. Troughs tell you the minimum drug coverage between doses. If troughs are very low relative to peaks, you have a wide "sawtooth" pattern, which split dosing can flatten.

Steady State

The point where the curve stops climbing and peaks/troughs become consistent. Before steady state, each dose adds to a rising baseline. After steady state, the amount going in equals the amount going out. This typically takes 4-5 half-lives of consistent dosing.^[7]

Dose Markers

Vertical markers on the chart show when each injection occurs. When you change doses (e.g., escalating from 4mg to 8mg), the markers help you see exactly when the transition begins and how quickly levels shift to the new steady state.

The chart is interactive. Hover over any point to see the exact modeled drug amount and time. Zoom in to specific weeks. Compare how different protocols produce different curve shapes by creating multiple schedules.

Multi-Dose Accumulation and Steady State

GLP-1 medications have long half-lives (5-7 days), which means each weekly dose is administered before the previous dose has fully cleared. This causes drug accumulation: each new dose adds to the remaining drug from prior doses.

The calculator handles this through superposition: at any time point, it calculates the remaining contribution from every previous dose and sums them. This produces the total drug amount in the body at each moment. Without superposition, a calculator would underestimate your actual drug levels by ignoring the carryover from previous doses.

Steady state is reached when the amount eliminated between doses equals the amount administered. For most GLP-1 medications, this takes approximately 4-5 weeks (4-5 half-lives) of consistent dosing at the same level. The calculator detects steady state by checking when trough-to-trough variation falls below 1%.^[7]

Half-life comparison chart showing retatrutide semaglutide and tirzepatide elimination rates

Comparison of half-lives across the three supported compounds. Longer half-lives mean slower elimination and more drug accumulation with repeated dosing.

Drug Parameters

The accuracy of any PK model depends on its input parameters. Here are the values GLP3Planner uses, with context for each:

Parameter	Retatrutide	Semaglutide	Tirzepatide
Half-life (days)	6.0^[1]	7.0^[4]	5.0^[5]
Bioavailability	0.95 (95%)^[6]	0.89 (89%)^[4]	0.80 (80%)^[5]
Volume of Distribution (L)	7.0^[6]	12.5^[4]	10.3^[5]
Absorption Rate (h^-1)	0.5	0.5	0.5
Mechanism	GLP-1/GIP/Glucagon triple agonist	GLP-1 receptor agonist	GLP-1/GIP dual agonist
FDA Status	Investigational (Phase 3)	Approved (Ozempic, Wegovy)	Approved (Mounjaro, Zepbound)
Steady State (approx.)	4-5 weeks	4-5 weeks	4-5 weeks

What These Parameters Mean

Half-life: How long it takes for the body to eliminate half the drug. Longer half-lives mean more accumulation and slower washout. Semaglutide's 7-day half-life produces more accumulation than tirzepatide's 5-day half-life at equivalent dosing intervals.
Bioavailability: The fraction of the injected dose that actually reaches the bloodstream. Retatrutide's 95% bioavailability means very little drug is lost at the injection site. Tirzepatide's 80% means a larger fraction does not make it into circulation.
Volume of distribution: A pharmacokinetic concept describing how widely the drug distributes throughout body tissues. Larger volumes mean the drug is more dispersed and diluted, resulting in lower peak concentrations per mg of dose.
Absorption rate: How quickly the drug moves from the injection site into the bloodstream. All three compounds use the same absorption rate constant (0.5 per hour) because subcutaneous absorption is similar across GLP-1 agonists.

Reconstitution Math (BAC Water → Syringe Units)

Before the PK model can plot anything, a compounded or research vial has to be reconstituted — the powder is dissolved in bacteriostatic (BAC) water so a measured dose can be drawn into a syringe. GLP3Planner's reconstitution calculator and dose-to-units calculator use the same three-step arithmetic. It is unit conversion, not a clinical claim, so we document it in full here.

Step	Formula	What it gives you
1. Concentration	concentration (mg/mL) = vial (mg) ÷ BAC water (mL)	How strong each mL of the mixed vial is.
2. Injection volume	volume (mL) = dose (mg) ÷ concentration (mg/mL)	How much liquid holds your dose.
3. Syringe units	units (U-100) = volume (mL) × 100	The mark to draw to on a U-100 insulin syringe.

The three steps collapse into a single expression:

units = (dose_mg ÷ (vial_mg ÷ bac_mL)) × 100

Worked Example

Reconstituting a 20 mg retatrutide vial with 3 mL of BAC water to draw a 2 mg dose:

Concentration = 20 mg ÷ 3 mL = 6.67 mg/mL
Volume = 2 mg ÷ 6.67 mg/mL = 0.30 mL
Units = 0.30 mL × 100 = 30 units on a U-100 syringe

Conventions Used

U-100 syringe: 100 units = 1 mL. This is the standard insulin-syringe marking, so multiplying the injection volume (mL) by 100 reads straight off the barrel. The markings are units, not International Units (IU).
BAC water: bacteriostatic water is sterile water with 0.9% benzyl alcohol added as a preservative, which lets a multi-dose vial be used over several weeks. The BAC volume only changes concentration — it does not change the total mg of drug in the vial.

For a step-by-step walkthrough with mixing and storage notes, see the retatrutide reconstitution guide, or run your own numbers in the reconstitution calculator.

Standard Titration Ladders

Titration means starting low and stepping the dose up on a fixed schedule so the body can adjust. Each ladder below steps up every 4 weeks; the final rung is the maintenance (target) dose and is held indefinitely. These are the reference schedules behind the titration calculator, which lets you pick any start and target rung to build a week-by-week plan.

These ladders are educational references drawn from the cited primary sources, not personalized prescriptions. Retatrutide is investigational and has no FDA-approved titration schedule. Always follow a clinician's plan for your own dosing.

Retatrutide^[1]

Start 2 mg → target 12 mg. Investigational; this reflects the Phase 2 trial escalation, not an approved label.

Step	Dose (mg)	Weeks at step	Notes
1	2	Weeks 1–4	Starting dose
2	4	Weeks 5–8
3	8	Weeks 9–12
4	12	Week 13 onward	Target / maintenance

Tirzepatide^[5]

Start 2.5 mg → up to 15 mg. Matches the Mounjaro/Zepbound label escalation.

Step	Dose (mg)	Weeks at step	Notes
1	2.5	Weeks 1–4	Non-therapeutic lead-in
2	5	Weeks 5–8	First maintenance option
3	7.5	Weeks 9–12
4	10	Weeks 13–16
5	12.5	Weeks 17–20
6	15	Week 21 onward	Maximum dose

Semaglutide (Wegovy weight-loss ladder)^[8]

Start 0.25 mg → target 2.4 mg. This is the Wegovy weight-management schedule — not Ozempic's type-2-diabetes ladder (0.25 → 0.5 → 1 → 2 mg).

Step	Dose (mg)	Weeks at step	Notes
1	0.25	Weeks 1–4	Non-therapeutic lead-in
2	0.5	Weeks 5–8
3	1	Weeks 9–12
4	1.7	Weeks 13–16
5	2.4	Week 17 onward	Maintenance / target

Build a personalized version — your own start dose, target, and interval — in the titration calculator.

See the Model in Action

Enter your doses and see what the model predicts. Compare protocols, visualize accumulation, find your steady state.

Open Calculator View Pre-Computed Scenarios

Model Limitations

No model perfectly predicts individual drug levels. Key limitations to understand:

Individual variation: PK parameters vary between people based on body composition, kidney and liver function, injection site, and genetics. The parameters above are population averages from clinical trials, not personalized values.
One-compartment simplification: Real drug distribution involves multiple tissue compartments. The one-compartment model captures the dominant behavior for weekly dosing but simplifies the initial distribution phase.
Retatrutide data is preliminary: As an investigational drug with no FDA-approved prescribing information, retatrutide PK parameters are estimated from Phase 2 trial publications.^[1] These may be refined as Phase 3 data becomes available.
No dose-response modeling: The calculator shows drug levels, not clinical effects. Blood levels do not linearly predict weight loss, appetite suppression, or side effects. Two people at the same drug level may have very different experiences.

The purpose of this tool is clarity, not clinical guidance. Seeing your modeled drug levels helps you understand accumulation, steady state, and what happens when you change doses. It does not replace the advice of a doctor who knows your individual health situation.

Technical Implementation

The PK engine is built in Python using NumPy and SciPy for numerical computation. Interactive charts are rendered with Plotly.js. Key implementation details:

Time resolution: Calculations run at 30-minute intervals for smooth curve rendering
Superposition: Each time point sums contributions from all previous doses, accounting for both absorption and elimination
Steady-state detection: The model iterates dosing intervals until trough-to-trough variation falls below 1%
Visualization: Plotly.js renders interactive charts with hover data, zoom, pan, and dose markers
Pre-computed scenarios: Common protocols are pre-calculated and served as static pages for faster loading. See the dosing scenarios library.

See Your Levels

Enter your doses and see what the model predicts for your schedule.

Open Calculator

Frequently Asked Questions

What pharmacokinetic model does GLP3Planner use?

GLP3Planner uses a one-compartment pharmacokinetic model with first-order absorption (the Bateman equation) for subcutaneous injection. Drug parameters including half-life, bioavailability, and volume of distribution are sourced from published Phase 2/3 clinical trial data for each compound. A simplified exponential decay model is also available for faster computation of peak and trough levels.

How accurate is the GLP3Planner calculator?

The calculator uses population-average parameters from clinical trials, so it models typical drug levels accurately for general patterns like accumulation and steady state timing. Individual variation exists based on body composition, kidney and liver function, and injection site. The model is most useful for understanding relative differences between protocols rather than predicting exact personal blood levels.

Where does GLP3Planner get its drug data?

Drug parameters come from published clinical trial data: the Phase 2 NEJM trial for retatrutide (Jastreboff et al., 2023), FDA prescribing information for semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound), and the STEP and SURMOUNT trial series. All sources are cited in the references section below with links to the original publications.

How does the calculator handle multiple doses?

The calculator uses superposition: at each time point, it calculates the remaining drug from every previous dose and sums them. This models how GLP-1 medications accumulate with weekly dosing due to their long half-lives (5-7 days), showing when steady state is reached and how levels change with dose adjustments.

Can I use this calculator for compounded peptides?

Yes. The pharmacokinetic model works the same regardless of whether you are using brand-name or compounded medications. The active compound is identical, so the half-life, absorption, and elimination parameters apply equally. The reconstitution calculator can also help you calculate syringe units for compounded vials.

Why does my chart show increasing levels even at the same dose?

That is drug accumulation in action. Because GLP-1 medications have long half-lives (5-7 days), each weekly dose is given before the previous one has fully cleared. The leftover drug adds to the new dose, causing levels to climb until steady state is reached. This is normal and expected. It typically takes 4-5 weeks at a consistent dose for levels to stabilize.

What is the difference between the Bateman model and the simple decay model?

The Bateman model includes the absorption phase (the time it takes for the drug to move from the injection site into the bloodstream), producing a more realistic curve that rises, peaks, and then declines. The simple decay model assumes the full dose is immediately in your system and only models elimination. For weekly dosing, the practical difference is small because absorption is fast relative to the dosing interval. Both models agree closely on peak and trough values.

Does body weight affect the calculator results?

The current model uses fixed population-average parameters and does not adjust for individual body weight. In reality, body composition can affect volume of distribution and elimination rate. A larger person may distribute the same dose across more tissue, resulting in somewhat lower peak concentrations. However, clinical trials dose all participants the same regardless of weight, so the population-average approach matches how these drugs are actually used.

References

Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-hormone-receptor agonist retatrutide for obesity: a Phase 2 trial. N Engl J Med. 2023;389(6):514-526. PubMed
Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. PubMed
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(4):327-340. PubMed
Novo Nordisk. Ozempic (semaglutide) prescribing information. U.S. Food and Drug Administration. FDA Label
Eli Lilly and Company. Mounjaro (tirzepatide) prescribing information. U.S. Food and Drug Administration. FDA Label
Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b trial. Lancet. 2022;400(10366):1869-1881. PubMed
StatPearls. Pharmacokinetics, Steady State. National Center for Biotechnology Information. NCBI Bookshelf
Novo Nordisk. Wegovy (semaglutide) injection prescribing information. DailyMed, U.S. National Library of Medicine. DailyMed

Medical Disclaimer

This page is for informational and educational purposes only. It does not constitute medical advice, diagnosis, or recommendations. The pharmacokinetic models described here produce estimates based on population-average clinical trial data and do not predict individual drug levels. Always consult your doctor before starting, adjusting, or stopping any medication.