What is the oral bioavailability of tablet furosemide (loop diuretic)?

Oral Bioavailability of Tablet Furosemide

The oral bioavailability of tablet furosemide is approximately 60-64% in healthy individuals, though this can vary substantially (ranging from 10% to nearly 100%) due to variable absorption, site-specific intestinal uptake, and first-pass metabolism. 1

Established Bioavailability Values

• In fasted healthy individuals, the mean bioavailability of furosemide tablets is 64%, while furosemide oral solution is 60%, compared to intravenous administration. 1
• The bioavailability range across individuals is highly variable, spanning from as low as 10% to nearly 100% in different patients. 2
• Individual patients can experience bioavailability variations ranging from 20% to 84% between different occasions, with maximal intraindividual variation documented from 20% to 61%. 3

Factors Contributing to Variable Bioavailability

Absorption Characteristics

• Furosemide exhibits incomplete, site-specific absorption in the gastrointestinal tract, which is not dissolution-rate limited but rather permeability-limited. 2, 4
• Intestinal transporters play a critical role: furosemide is a substrate of OATP2B1 (uptake transporter), BCRP, and MRP4 (efflux transporters), which significantly influence its intestinal permeability and absorption. 2
• The drug demonstrates poor passive permeability, requiring transporter-mediated uptake to achieve clinically observed absorption levels. 2

First-Pass Metabolism

• Approximately 20-30% of an oral furosemide dose undergoes presystemic first-pass metabolism in the gastrointestinal wall, primarily in the stomach. 4
• Furosemide glucuronide is the major biotransformation product, with 53.9% of the oral dose excreted as glucuronide conjugate compared to 34.2% after intravenous injection, indicating substantial first-pass glucuronidation. 5
• Gastric metabolic activity for furosemide is 5-10.5 fold greater than hepatic or small intestinal metabolism, making gastric first-pass metabolism a major contributor to incomplete bioavailability. 4
• Hepatic first-pass elimination is minimal, estimated at less than 6-10%. 4

Clinical Implications in Disease States

Heart Failure Patients

• Patients with heart failure may experience reduced oral bioavailability due to intestinal edema (bowel wall edema), making intravenous administration more reliable in acute decompensation. 6
• Despite potential absorption variability, oral furosemide demonstrates good bioavailability in stable cirrhotic patients, making oral administration the preferred route to avoid acute reductions in glomerular filtration rate associated with intravenous dosing. 6

Chronic Respiratory Failure

• Patients with chronic respiratory failure demonstrate significantly lower bioavailability (mean absolute bioavailability 41.3% based on unchanged drug, 63.4% including glucuronide conjugate) compared to healthy subjects. 5
• Mean 24-hour urinary recovery of unchanged furosemide was only 11.5 mg in respiratory failure patients versus 14.4 mg in healthy controls after a 40 mg oral dose. 5
• Enhanced glucuronidation and incomplete drug absorption account for the reduced bioavailability in these patients. 5

Pharmacokinetic Considerations

• Peak plasma concentrations occur within 1-2 hours after oral administration, with onset of diuresis within 1 hour and duration of effect lasting 6-8 hours. 1
• The mean absorption time is approximately 87-128 minutes for tablets, significantly longer than the mean residence time after intravenous dosing (57 minutes), confirming that absorption is the rate-limiting step. 3
• Furosemide is 91-99% bound to plasma proteins (primarily albumin) at therapeutic concentrations, with only 2.3-4.1% remaining unbound. 1

Important Clinical Caveats

• The extensive intraindividual and interindividual variability in furosemide bioavailability means that dosing must be titrated based on clinical response (weight loss, urine output, symptom relief) rather than assuming consistent absorption. 3
• Significantly more furosemide is excreted unchanged in urine following intravenous injection compared to oral administration, reflecting the incomplete bioavailability of oral formulations. 1
• Food effects and timing of administration can further influence absorption, though single morning dosing is recommended for compliance in chronic management. 6
• Alternative loop diuretics like bumetanide and torsemide exhibit greater oral bioavailability than furosemide, which may explain superior clinical responses in some patients. 6