Treatment of hypercalcemia in parathyroid cancer with WR-2721, S-2-(3-aminopropylamino)ethyl-phosphorothioic acid.
The chemoprotective and hypocalcemic agent WR-2721, S-2-(3-aminopropylamino) ethyl-phosphorothioic acid, inhibits parathyroid hormone secretion in vivo and in vitro. We report the first clinical use of WR-2721 in refractory hypercalcemia secondary to parathyroid cancer. After several days of saline diuresis the patient received WR-2721, 740 mg/m2 over 15 minutes, resulting in a fall in serum calcium from 11.76 to 9.06 mg/dL within 24 hours. Serum parathyroid hormone levels decreased from 675 to 140 microLeq/mL 2 hours after the infusion was complete. When hypercalcemia recurred the patient was retreated with differing doses and infusion rates to determine the optimal method of drug administration to provide a satisfactory hypocalcemic response without adverse effects. In this patient, WR-2721 in intravenous boluses of 150 mg/m2 was effective without adverse effects. Using high-pressure liquid chromatography with electrochemical detection, plasma pharmacokinetic studies showed that WR-2721's distribution half-life is 0.55 minutes.
Glover
D J
DJ
Shaw
L
L
Glick
J H
JH
Slatopolsky
E
E
Weiler
C
C
Attie
M
M
Goldfarb
S
S
D000236:Adenoma / Q000097:blood / Q000150:complications; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood; D010282:Parathyroid Neoplasms / Q000097:blood* / Q000150:complications
D009946:Organothiophosphorus Compounds; D010281:Parathyroid Hormone; D004999:Amifostine