Transplacental treatment of fetal tachycardia: implications of drug transporting proteins in placenta.
Sustained fetal tachyarrhythmia (> 180 bpm) is a potentially life-threatening condition for the unborn. Digoxin is commonly used as an initial monotherapy. Flecainide, sotalol, and verapamil are also used as a monotherapy or a combination therapy with digoxin. The treatment success rate with digoxin is about 50%. Presence of hydrops is associated with poor placental transfer of digoxin. Although transplacental pharmacotherapy has been available, it is a challenging task to maximize fetal drug exposure, while minimizing drug exposure of the mother. In addition, clear evidence behind drug of choice and treatment algorithm is lacking. Whereas prospective clinical studies with rigorous design remain to be seen, our knowledge on placental drug transport at a molecular level has been steadily increasing. For example, an ATP-dependent membrane protein, known as P-glycoprotein, is expressed in placenta, decreasing fetal exposure to maternal digoxin. Pharmacological manipulation of drug transporters may open a door to ultimate optimization of the transplacental pharmacotherapy.
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Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002352:Carrier Proteins / Q000378:metabolism*; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005315:Fetal Diseases / Q000188:drug therapy*; D006801:Humans; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013610:Tachycardia / Q000188:drug therapy*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000889:Anti-Arrhythmia Agents; D002352:Carrier Proteins; D004077:Digoxin