From the Guidelines
Rocuronium is primarily eliminated through hepatic uptake and biliary excretion, with minimal renal clearance, and its clearance is reduced in renal failure patients and cirrhotic patients. The drug's elimination is mainly through the liver, with about 30-40% of the drug excreted unchanged in bile, while a small portion (10-20%) undergoes metabolism in the liver to produce less active metabolites 1. The remainder is excreted in urine, with only about 10-20% of the administered dose eliminated through the kidneys. This predominantly hepatic clearance mechanism explains why patients with liver dysfunction may experience prolonged neuromuscular blockade, while those with renal impairment generally show less significant changes in rocuronium's duration of action.
The pharmacokinetics of rocuronium are affected in patients with renal or hepatic failure, resulting in extended duration of action of the drug, particularly with repeated injections or continuous infusion 1. However, the initial dose of rocuronium does not need to be modified in renal or hepatic failure patients, as the time to onset of action remains unchanged, and the efficacy of the initial dose is only slightly reduced in cirrhotic patients 1.
Key points to consider when using rocuronium in patients with renal or hepatic impairment include:
- The drug's elimination half-life is approximately 60-120 minutes in healthy adults, which contributes to its intermediate duration of action as a neuromuscular blocking agent.
- Patients with hepatic impairment may require dose adjustments or more careful monitoring due to the risk of prolonged neuromuscular blockade.
- Patients with renal dysfunction typically require less modification of standard dosing regimens, as the drug's clearance is less affected by renal impairment. It is essential to consider these factors when using rocuronium in clinical practice to ensure optimal patient outcomes and minimize the risk of adverse effects 1.
From the FDA Drug Label
Studies of distribution, metabolism, and excretion in cats and dogs indicate that rocuronium is eliminated primarily by the liver. The effects of renal failure and hepatic disease on the pharmacokinetics and pharmacodynamics of rocuronium in humans are consistent with these findings
- Main method of clearance: The liver is the primary organ responsible for the elimination of rocuronium.
- Key points:
- Rocuronium is primarily eliminated by the liver.
- Hepatically impaired patients may have a longer clinical duration due to a large increase in volume of distribution.
- Renal failure has a small effect on the clearance of rocuronium, which is offset by an increase in volume of distribution 2
From the Research
Rocuronium Clearance Methods
- Rocuronium is mainly excreted by the liver, but its clearance also involves the kidneys and bile [ 3 ].
- The drug is taken up by the liver and excreted into bile in high concentrations, with faecal and urinary excretion being the major routes of elimination [ 4 ].
- In patients with severe renal impairment, rocuronium clearance is not significantly affected, and sugammadex can be used for reversal of neuromuscular blockade [ 5 ].
- In cases of chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced by upregulation of Oatp2 [ 6 ].
Excretion Routes
- Urinary excretion: 26% of the dose is recovered in the urine within 48 hours [ 4 ].
- Biliary excretion: 7% of the dose is recovered in the bile within 48 hours [ 4 ].
- Faecal excretion: 31% of the dose is recovered in the faeces over 4-8 days [ 4 ].