Induction of prostaglandin synthesis as the mechanism responsible for the chills and fever produced by infusing amphotericin B.
Amphotericin B produces chills and fever in a significant proportion of patients who receive this drug. The mechanism for this adverse effect is unknown. Amphotericin B suspension at a concentration of 1.0 microgram/ml was demonstrated to be a potent inducer of prostaglandin E2 synthesis by human and murine mononuclear cells in vitro. A double-blind, placebo-controlled clinical trial demonstrated that ibuprofen (10 mg/kg), a potent inhibitor of prostaglandin synthesis, administered 30 min before amphotericin B administration reduced the incidence of chilling from 87% to 49% (P = .01); the incidence of chilling reactions considered severe was reduced from 69% to 15% (P = .008). We postulate that the chills and fever produced by an infusion of amphotericin B are mediated through prostaglandin E2 synthesis. Ibuprofen is therapeutically useful in ameliorating the chills and fever caused by amphotericin B.
Gigliotti
F
F
Department of Child Health Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Shenep
J L
JL
Lott
L
L
Thornton
D
D
D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D015232:Dinoprostone; D004311:Double-Blind Method; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D007263:Infusions, Parenteral; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D011458:Prostaglandins E / Q000096:biosynthesis*; D012768:Shivering / Q000187:drug effects*
D011458:Prostaglandins E; D000666:Amphotericin B; D015232:Dinoprostone; D007052:Ibuprofen