Abstract | BACKGROUND: METHODS: Six dogs were anesthetized with pentobarbital to a sufficient depth that spontaneous and reflex muscle movements were absent. Their tracheas were intubated, their lungs were mechanically ventilated, and they received round-the-clock intensive medical and nursing care for 3 weeks. Transduced gastrocnemius muscle responses to metocurine were determined weekly. A 4- to 15-min infusion of 148-4,300 microg/min (longer durations and greater concentrations on progressive weeks) yielded more than 80% paralysis. Serial metocurine plasma concentrations during the onset of the block and recovery provided data to determine pharmacokinetics using NONMEM. Metocurine plasma concentrations and the degree of paralysis were used to model the effect compartment equilibration constant, and the Hill equation was used to yield the slope factor and potency within the effect compartment. RESULTS: The metocurine effect compartment concentration associated with a 50% diminution of twitch height after 3 weeks was 1,716+/-1,208 ng/ml (mean +/- SD), which was significantly different from 257+/-34 ng/ml, the value on day 0. There were no pharmacokinetic differences. CONCLUSION:
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Authors | G A Gronert, D L Fung, S C Haskins, E P Steffey |
Journal | Anesthesiology
(Anesthesiology)
Vol. 90
Issue 6
Pg. 1741-5
(Jun 1999)
ISSN: 0003-3022 [Print] United States |
PMID | 10360874
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Neuromuscular Nondepolarizing Agents
- metocurine
- Tubocurarine
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Topics |
- Animals
- Dogs
- Drug Resistance
- Intensive Care Units
- Muscle, Skeletal
(drug effects)
- Neuromuscular Nondepolarizing Agents
(pharmacology)
- Respiration, Artificial
- Time Factors
- Tubocurarine
(analogs & derivatives, pharmacokinetics, pharmacology)
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