Bioavailability vs serum concentration

Why the same milligrams in two people can produce different serum levels, what bioavailability adds to the picture, and how to interpret the DoseCurve chart in light of that.

When two people inject the same milligrams of the same drug at the same schedule and their bloodwork comes back markedly different, the usual reason is some combination of three variables: bioavailability, volume of distribution and clearance. DoseCurve does not estimate any of them. This page explains what bioavailability is, why injectable formulations are not automatically 100% bioavailable, and how that interacts with the chart's milligram-remaining display.

This is educational background. It does not recommend any compound, dose, route or formulation, and it does not interpret anyone's individual bloodwork.

What bioavailability is

Bioavailability — usually written F — is the fraction of an administered dose that reaches the systemic circulation in active form. By convention, intravenous administration is defined as F = 1.0 (100%). Every other route is some fraction less.

F = (AUC after route X) / (AUC after IV)

AUC is "area under the curve" — total exposure to the drug. The bioavailability of a route or formulation is essentially the ratio of total exposure compared to giving it directly into a vein.

Why injectables are not all F = 1

Intravenous injection is the only route that genuinely delivers the full dose to the bloodstream instantly. Every other injectable route involves some absorption step that is less than perfect:

Intramuscular oil depot. The ester releases over days to weeks from the depot. Some fraction is metabolised at the injection site before reaching circulation. Some fraction may diffuse into surrounding tissues without entering the bloodstream as the labelled compound. Typical IM ester bioavailability for testosterone esters is in the 0.85–0.95 range based on published comparisons to IV testosterone.
Subcutaneous depot. Slightly slower release, similar overall bioavailability for most oil-based formulations.
Subcutaneous aqueous (peptides, GLP-1s). Bioavailability can vary more widely. Larger peptides may have F values in the 0.4–0.9 range depending on the molecule.
Inhaled, intranasal, sublingual, transdermal. All have their own characteristic bioavailability profiles, generally lower than parenteral routes.
Oral. First-pass hepatic metabolism makes oral bioavailability of many compounds very low — testosterone undecanoate orally is roughly F = 0.05–0.10, which is why oral T is dosed in multi-hundred-milligram amounts compared to single-digit milligrams equivalent intramuscular.

How F interacts with the chart

The DoseCurve chart plots administered milligrams, not bioavailable milligrams. When you log a 100 mg injection, the chart adds 100 mg to the running total and decays it. If the real bioavailability is 0.9, the actual systemic exposure is 90 mg, and the "true" curve sits about 10% lower than the displayed one.

You could in principle apply an F correction yourself by entering a smaller dose. We deliberately do not do this for you, for two reasons:

The right F value is formulation-specific and individual-specific. Applying a fixed factor would be a false precision.
The chart is meant to be a model of the dosing schedule, not a prediction of serum concentration. Bloodwork is the only reliable way to anchor absolute values.

Why two people on the same dose get different bloodwork

The chain from "mg injected" to "ng/dL measured at the lab" passes through:

Bioavailability (F). Different absorption fraction by formulation and injection technique.
Volume of distribution (Vd). Different body composition, fluid status, protein binding.
Clearance. Different hepatic enzyme activity, renal function, drug interactions, age.
Sampling timing. When in the cycle the blood draw happened relative to the most recent dose.
Assay differences. Lab-to-lab variation in measurement technique and reference ranges.
Active metabolite handling. What the assay actually measures (total testosterone vs free vs bioavailable, for example).

Any of those can shift a measured serum level by 20–40% in either direction. Combine two or three and the same protocol can look entirely different on paper for two people.

What the chart is good for, given all that

Even though the chart cannot predict your bloodwork, it is still useful for:

Comparing options. If switching from once-weekly to twice-weekly at the same total dose flattens the chart, it will flatten your real curve too, roughly in proportion.
Timing decisions. The chart will accurately tell you that a long ester takes much longer to reach steady state than a short ester, regardless of your individual Vd.
Spotting outliers. A missed dose, a doubled dose, or a schedule shift produces a visible local effect on the chart that you can use to interpret an unexpected bloodwork result.
Communicating with a prescriber. Showing a clinician the modelled curve and your bloodwork together is often more productive than describing the schedule verbally.

What it is not good for

Reverse-engineering a target serum level into a dose. That requires F, Vd and clearance estimates the model does not have.
Comparing absolute heights between users. The chart's heights are model outputs, not measurements.
Replacing bloodwork. Especially for hormones with feedback regulation (testosterone, GH, etc.), modelled exposure is not the same as biological effect.

How to anchor the chart with one bloodwork point

If you do have a lab value at a known time relative to your last injection, you can use it to calibrate your mental sense of where the chart sits. Read the modelled mg-remaining at the time of the draw, divide your measured ng/dL by that number, and you have a personal ng/dL-per-mg conversion that applies as long as your formulation, schedule and physiology are stable. It is not a substitute for repeat labs, but it lets you read subsequent chart changes in approximate serum-equivalent terms.

This is a thinking aid. It is not a recommendation to adjust dose based on the calculation.