Effect of phenytoin on meperidine clearance and normeperidine formation.
The presystemic metabolism of meperidine to normeperidine was examined in four healthy men before, during, and 3 wk after phenytoin. The results from the two control periods were similar. Meperidine systemic clearance rose from 1017 +/- 225 ml/min (mean +/- SD) to 1280 +/- 130 ml/min during phenytoin dosing (P less than 0.01). Meperidine elimination half-life fell from 6.4 +/- 1.0 hr to 4.3 +/- 0.4 hr during phenytoin dosing (P less than 0.05). Bioavailability fell from 0.61 +/- 0.08 to 0.43 +/- 0.14 (P less than 0.07). Meperidine volume of distribution, renal clearance, and protein binding did not change. The normeperdine area under the blood concentration-time curve from 0 to 24 hr after intravenous meperidine rose from 385 +/- 105 ng/hr/ml-1 to 589 +/- 108 ng/hr/ml-1 during phenytoin dosing (P less than 0.01); after oral meperidine it rose from 592 +/- 50 ng/hr/ml-1 to 738 +/- 178 ng/hr/ml-1. Normeperidine renal clearance was approximately four times that of meperidine, but was not altered by phenytoin. Because analgesia relates to meperidine blood concentrations, patients on long-term phenytoin therapy may require more frequent parenteral doses and larger and more frequent oral doses than usual.
D000328:Adult; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008614:Meperidine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology*
D010672:Phenytoin; D008614:Meperidine; C002752:normeperidine