Pharmacokinetics of misoprostol in the elderly, in patients with renal failure and when coadministered with NSAID or antipyrine, propranolol or diazepam.
The pharmacokinetics of misoprostol were examined in the following contexts: in coadministration with the nonsteroidal antiinflammatory agents (NSAID) aspirin, diclofenac, ibuprofen, indomethacin and piroxicam; in coadministration with agents extensively metabolized by the liver--i.e., antipyrine, propranolol and diazepam; in healthy elderly subjects; and in patients with various degrees of renal failure. No clinically important interactions between misoprostol and NSAID were observed. Similarly, no metabolic interactions between misoprostol and antipyrine, propranolol or diazepam were noted. Pharmacokinetic variable values in elderly subjects did not differ in a clinically significant manner from those in younger subjects. Finally, although values for some pharmacokinetic variables--maximum concentration of misoprostol acid, area under the concentration-time curve and elimination half-life--were increased in patients with renal failure compared with controls, these alterations do not warrant changes in misoprostol dosage. These factors are particularly relevant to safety of misoprostol administration in elderly individuals, who not only consume more NSAID than young adults, but are also more likely to have intercurrent nonarthritic illness requiring additional medication and potentially modifying drug kinetics.
Nicholson
P A
PA
Searle Research and Development, Skokie, IL 60071.
Karim
A
A
Smith
M
M
D000328:Adult; D000368:Aged; D000375:Aging / Q000187:drug effects*; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D000983:Antipyrine / Q000493:pharmacokinetics; D003975:Diazepam / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D016595:Misoprostol; D011433:Propranolol / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016595:Misoprostol; D011433:Propranolol; D000527:Alprostadil; D003975:Diazepam; D000983:Antipyrine