Pharmacokinetics and pharmacodynamics of d-tubocurarine and metocurine in the elderly.
The effects of age (older than 70 yr) on the pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) and metocurine (MTc) were evaluated in studies of 21 patients aged 70-87 and 21 patients aged 29-59. There was a significant difference in the pharmacokinetic parameters of all elderly patients compared with younger controls. With both dTc and MTc, the elderly exhibited a decreased plasma clearance, decreased initial volume of distribution, decreased volume of distribution, and a prolonged elimination half-life. After 0.3 mg/kg of dTc, the times for 50% return of twitch and recovery index (25-75% return of twitch response) in the elderly were significantly longer than in the young (P less than 0.02). A similar observation was made for the elderly patients receiving 0.15 mg/kg of MTc. No significant difference was seen in the log plasma concentration-twitch response relationship between 20-80% paralysis in young and in elderly patients receiving dTc. There was a similar lack of significant difference between the log plasma concentration-twitch response lines for elderly and young patients receiving MTc. Because there was no difference between the plasma concentration-response relationships in the elderly and young, altered sensitivity to dTc or MTc cannot explain the longer duration of action seen in the elderly. The most likely explanation for this difference is the altered pharmacokinetics of these two drugs in the elderly.
D000328:Adult; D000367:Age Factors; D000368:Aged; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000378:metabolism*; D014403:Tubocurarine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D009466:Neuromuscular Blocking Agents; C032943:metocurine; D014403:Tubocurarine