What is the bioavailability of levothyroxine IV to PO?: Understanding Dose Conversion and Clinical Differences

October 14, 2025 •

4 min read

Oral levothyroxine's bioavailability is estimated to be between 60% and 80%, substantially lower than the 100% achieved with intravenous administration. This critical distinction helps explain what is the bioavailability of levothyroxine IV to PO and dictates the necessity of dose adjustments when a patient's route of administration changes.

Quick Summary

A comparison of intravenous and oral levothyroxine pharmacokinetics reveals that intravenous administration provides 100% bioavailability, whereas oral absorption is variable and incomplete. This difference necessitates precise dose adjustments and dictates the appropriate clinical application for each route of administration.

Key Points

Bioavailability Difference: Intravenous (IV) levothyroxine has 100% bioavailability, while oral (PO) bioavailability is typically 60-80% due to incomplete absorption and first-pass metabolism.
Dose Conversion Ratio: When converting from an IV dose to an oral dose, the oral dose needs to be higher. A common conversion is IV dose ≈ 75-80% of the oral dose, or conversely, PO dose ≈ 1.25-1.33 times the IV dose.
Factors Affecting Oral Absorption: Numerous factors can alter oral levothyroxine absorption, including food, timing of dose, GI disorders (e.g., celiac disease), and other medications (e.g., antacids, calcium, iron, PPIs).
Clinical Indications for IV: The intravenous route is typically reserved for critically ill patients (like those with myxedema coma) or individuals who cannot absorb or take oral medication for an extended period.
Patient Monitoring: Clinical and laboratory monitoring (TSH, free T4) is crucial after switching between IV and PO formulations to ensure therapeutic stability and prevent adverse effects.
Drug Half-Life: Levothyroxine has a long half-life of 7-10 days, which is important because missing a few oral doses may not cause an immediate significant change in thyroid hormone levels.

What Is Bioavailability and Why It Matters for Levothyroxine

Bioavailability refers to the proportion of a drug that enters the circulation when introduced into the body and is able to have an active effect. In simple terms, it measures how much of the drug gets where it needs to go. The route of administration is the most significant factor affecting a drug's bioavailability. For levothyroxine, the contrast between the intravenous (IV) and oral (PO) routes is dramatic and clinically crucial.

Intravenous (IV) Levothyroxine: When levothyroxine is administered directly into the bloodstream via an IV, it bypasses the entire digestive system. Therefore, 100% of the dose is immediately available to the body. There is no loss due to incomplete absorption or metabolism. This is the reason IV administration is reserved for critically ill patients or those unable to take oral medications.
Oral (PO) Levothyroxine: Oral administration involves a more complex process. The drug must first be dissolved, then absorbed from the gastrointestinal (GI) tract, primarily in the jejunum and ileum. Even after absorption, it may undergo some 'first-pass' metabolism in the liver before entering systemic circulation. These factors result in a significantly lower and more variable bioavailability for oral levothyroxine, typically ranging from 60% to 80% in most patients.

The Factors that Cause Variability in Oral Absorption

The non-100% bioavailability of oral levothyroxine is not a fixed percentage and can vary considerably among individuals and even in the same person on different days. This variability is influenced by a number of factors, including:

Timing of Administration: Taking oral levothyroxine with food, especially breakfast, can significantly decrease its absorption. For optimal absorption, it is recommended to take the medication on an empty stomach, at least 30-60 minutes before food.
Gastrointestinal Disorders: Conditions that affect the GI tract can impede levothyroxine absorption. Examples include celiac disease, lactose intolerance, atrophic gastritis, and Helicobacter pylori infection.
Other Medications and Supplements: Many drugs can interfere with levothyroxine absorption. This is especially true for substances that bind to levothyroxine in the gut, making it unavailable for absorption. Common examples include:
- Calcium and iron supplements
- Proton pump inhibitors (PPIs) and antacids (containing aluminum hydroxide)
- Bile acid sequestrants (e.g., cholestyramine)
- Phosphate binders
Age and Weight: Absorption of levothyroxine can change with age, with a slight decrease noted in those over 70. Additionally, the dose required often depends on a patient's body weight, and some research suggests that using actual body weight alone may lead to overdosing in overweight and obese individuals.

Converting Levothyroxine IV to PO: The Dose Adjustment

Because of the dramatic difference in bioavailability, converting a patient from IV to PO levothyroxine is not a one-to-one swap. A higher oral dose is required to achieve the same therapeutic effect as the IV dose. This is a critical step in managing patients transitioning from hospital care to home, or when their clinical status allows for oral medication.

Recommended Conversion Ratio: Many clinical guidelines recommend converting from an IV dose to an oral dose by using a 1:1.25 or 1:1.33 ratio, which is equivalent to giving an IV dose that is approximately 75% to 80% of the oral dose. For example, if a patient was on 100 mcg of oral levothyroxine, the equivalent IV dose would be around 75-80 mcg. Conversely, a 75 mcg IV dose would require a return to the initial 100 mcg PO dose.
Monitoring is Essential: Post-conversion, vigilant monitoring of thyroid function tests (specifically TSH and free T4) is essential to ensure the patient remains in a euthyroid state. TSH levels should be checked a few weeks after initiating oral therapy, and dose adjustments should be made as necessary based on laboratory results and clinical response.

Comparing IV and PO Levothyroxine


Feature	Intravenous (IV) Levothyroxine	Oral (PO) Levothyroxine
Bioavailability	100%	Variable (60-80% on average)
Route of Administration	Direct injection into a vein	Taken by mouth (tablet, capsule, or solution)
Onset of Action	Rapid (within 6-8 hours for effect)	Gradual (3-5 days for detectable effect, weeks for full stability)
Indications	Critically ill patients (e.g., myxedema coma, NPO status, severe malabsorption)	Standard, long-term maintenance therapy for hypothyroidism
Dosing	Calculated as a percentage (typically 75-80%) of the usual oral dose	Patient-specific, based on weight, age, and clinical response
Cost	Much higher due to preparation and administration resources	More cost-effective for long-term use
Cardiac Risk	Higher risk of cardiac complications, particularly in elderly or cardiovascular patients	Lower risk when used for maintenance and properly monitored

Clinical Applications of Bioavailability Knowledge

The long half-life of levothyroxine (7-10 days) means that even if a patient misses a few oral doses, their hormone levels will not immediately crash. This can make it unnecessary to convert to IV therapy for brief periods when oral intake is not possible, such as during a short NPO period for a hospital procedure. The decision to use IV levothyroxine is based on the clinical severity and duration of the inability to take oral medication.

For patients with malabsorption issues, such as those with celiac disease or who have undergone certain types of bariatric surgery, achieving stable thyroid levels with oral medication can be challenging. In such cases, alternative strategies might be necessary, including using liquid formulations or, in rare severe cases, parenteral administration.

Conclusion: The Importance of Precision in Thyroid Replacement

The difference in bioavailability between IV and PO levothyroxine is a cornerstone of effective medication management for patients with hypothyroidism. The 100% bioavailability of the intravenous form allows for a predictable and rapid therapeutic effect in critical situations like myxedema coma, but it also necessitates a lower dose to avoid cardiac complications. Conversely, the more variable oral bioavailability requires clinicians to meticulously manage dosage based on a range of patient-specific and environmental factors. Recognizing and accounting for these differences, particularly during dose conversion, is paramount for ensuring patient safety and therapeutic success. Consistent monitoring of TSH and free T4 levels remains the gold standard for navigating these adjustments with precision. For further information on managing complex levothyroxine cases, consulting authoritative resources such as the National Institutes of Health (NIH) is recommended.

Frequently Asked Questions

The oral dose of levothyroxine is higher than the intravenous dose because oral administration has a lower bioavailability. The oral medication must pass through the gastrointestinal tract, where some is not absorbed, and undergo first-pass metabolism in the liver before entering circulation. The IV route bypasses these processes, so 100% of the dose is immediately available.

When converting from an oral dose to an intravenous dose, the IV dose should be approximately 75% to 80% of the patient's stable oral dose. For example, a patient on 100 mcg of oral levothyroxine would typically receive a 75-80 mcg IV dose.

The absorption of oral levothyroxine can be reduced by food (especially dietary fiber, soy, and coffee), certain medications (including calcium supplements, iron supplements, antacids, and proton pump inhibitors), and specific gastrointestinal conditions like celiac disease or H. pylori infection.

IV levothyroxine is used for specific clinical situations where oral administration is not feasible. This includes treating critically ill patients, especially those in myxedema coma, patients who are unable to take oral medications (NPO), or those with severe malabsorption issues.

After converting a patient from IV back to oral levothyroxine, thyroid function tests, specifically TSH and free T4 levels, must be closely monitored. These tests should be performed a few weeks after the switch, and the oral dose should be adjusted as needed based on the results and the patient's clinical response.

No, it is not safe to assume a 1:1 conversion. Using a 1:1 ratio when switching from oral to IV levothyroxine could lead to overdosing and potential cardiac complications due to the higher bioavailability of the IV form. Conversely, a 1:1 switch from IV to PO would likely result in underdosing.

Oral levothyroxine is the preferred long-term treatment for hypothyroidism because it is more convenient, less expensive, and safer for maintenance therapy. The IV route carries higher costs, requires more resources for administration, and poses greater risks, particularly cardiac complications in certain populations.