Bromhexine Elimination Method
Bromhexine is eliminated primarily through hepatic metabolism with extensive first-pass effect (approximately 75-92%), while renal excretion of unchanged drug is negligible (<1% of the dose), making it safe to use in patients with renal impairment without dose adjustment.
Primary Elimination Pathway
Hepatic metabolism is the dominant elimination route for bromhexine, with an estimated hepatic extraction ratio of 0.92, indicating that approximately 92% of the drug is cleared during its first pass through the liver 1.
The extensive first-pass effect results in very low systemic bioavailability of only 1.8-3.9% after oral administration, with both hepatic and intestinal first-pass clearance contributing to this poor bioavailability 1.
Bromhexine follows a two-compartment pharmacokinetic model with a biological half-life of approximately 6 hours and a terminal elimination half-life of 8.9-11 hours due to its large volume of distribution rather than enterohepatic recycling 1, 2.
Renal Elimination (Minimal)
Renal clearance of unchanged bromhexine is negligible, with urinary excretion accounting for less than 1% of the administered dose over 24-30 hours 1, 2.
In bile duct cannulated rats, biliary excretion contained only 1.5% of the dose as intact and conjugated bromhexine within 30 hours, confirming that enterohepatic recycling does not contribute significantly to the drug's elimination profile 1.
Clinical Implications for Renal Impairment
No dose adjustment is required in patients with renal insufficiency because bromhexine elimination does not depend on kidney function 1, 2.
Studies in diabetic patients with varying degrees of albuminuria (including macroalbuminuria) showed no effect on renal function parameters, with creatinine clearance and beta-2-microglobulin excretion remaining unchanged after one month of bromhexine therapy 3.
This contrasts sharply with renally eliminated drugs like amantadine (90% renal excretion) or aminoglycosides (essentially 100% renal excretion), which require substantial dose adjustments or interval extensions when creatinine clearance falls below 30 mL/min 4.
Pharmacokinetic Considerations
The plasma concentration-time profile remains consistent regardless of biliary function, indicating that the slower terminal elimination is due to small plasma clearance and large distribution volume rather than biliary recycling 1.
Maximum plasma concentrations occur approximately 1.0-1.3 hours after oral administration, with area under the curve values of 132-140 nmol·L⁻¹·h 2.