Abstract | BACKGROUND: Recent trials indicate that rapacuronium's pharmacokinetic characteristics are influenced by both renal failure and cirrhosis but the time course of a single bolus dose of 1.5 mg/kg is affected minimally. The authors reassessed these pharmacokinetic findings and examined the time course of the same bolus dose followed by a 30-min infusion. METHODS: During nitrous oxide- isoflurane anesthesia, patients with normal renal and hepatic function (n = 25), those with renal failure (n = 28), and those with cirrhosis (n = 6) received a bolus dose of rapacuronium (1.5 mg/kg) followed by a 30-min infusion adjusted to maintain 90-95% twitch depression. At 25% recovery, neostigmine was administered. Blood was sampled until 8 h after the infusion to determine concentrations of rapacuronium and its active metabolite ORG9488. Rapacuronium's pharmacokinetic parameters were determined using mixed-effects modeling. RESULTS: Onset and facilitated recovery of twitch depression were similar in the three groups. Patients with renal failure required 22% less rapacuronium to maintain target twitch depression during the infusion. Rapacuronium's plasma clearance was 24% smaller in renal failure and decreased 0.5%/yr of age; rapid distribution clearance was 51% smaller in men than in women. After the infusion, ORG9488 concentrations decreased markedly more slowly in patients with renal failure. Cirrhosis did not alter the pharmacokinetics of rapacuronium. CONCLUSION:
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Authors | D M Fisher, G A Dempsey, D P Atherton, R Brown, A Abengochea, J M Hunter |
Journal | Anesthesiology
(Anesthesiology)
Vol. 93
Issue 6
Pg. 1384-91
(Dec 2000)
ISSN: 0003-3022 [Print] United States |
PMID | 11149430
(Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anesthetics, Inhalation
- Neuromuscular Nondepolarizing Agents
- Org 9488
- Vecuronium Bromide
- rapacuronium
- Nitrous Oxide
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Topics |
- Adolescent
- Adult
- Age Factors
- Aged
- Anesthetics, Inhalation
- Female
- Humans
- Kidney Failure, Chronic
(metabolism)
- Liver Cirrhosis
(metabolism)
- Male
- Middle Aged
- Neuromuscular Junction
(drug effects)
- Neuromuscular Nondepolarizing Agents
(administration & dosage, pharmacokinetics, pharmacology)
- Nitrous Oxide
- Time Factors
- Vecuronium Bromide
(administration & dosage, analogs & derivatives, pharmacokinetics, pharmacology)
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