Effect of amiodarone on the phospholipid and lamellar body content of lymphoblasts in vitro and peripheral blood lymphocytes in vivo.
Amiodarone is useful for the treatment of ventricular arrhythmias but has been associated with a significant degree of toxicity especially to lung and liver. The drug produces phospholipid accumulation in multilamella lysosomal inclusions in many tissues due to the ability of amiodarone and desethylamiodarone to inhibit phospholipase A. The adverse effects do not correlate with the plasma levels of amiodarone but relate more closely to the cumulative dose. No clear way of predicting amiodarone toxicity has yet emerged. In this report, normal human lymphoblasts in tissue culture were shown by electron microscopy to have dose-dependent increases in multilamellar inclusions when grown with amiodarone at concentrations which are routinely observed in patients receiving the drug. The content of phospholipid also increased but this parameter was not as sensitive as the number of multilamellar inclusions. Finally, lymphocytes from patients treated with amiodarone were examined by electron microscopy and shown to have increased numbers of multilamellar bodies.
Hostetler
K Y
KY
Department of Medicine, University of California, San Diego 92093.
Vande Berg
J
J
Aldern
K A
KA
Brophy
G T
GT
D000638:Amiodarone / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D010743:Phospholipids / Q000378:metabolism*
D010743:Phospholipids; D000638:Amiodarone