Treatment of clinically normal and cystinuric dogs with 2-mercaptopropionylglycine.
In a pharmacokinetic and tolerance study, 2 healthy Beagles were given 13.2 to 39.5 mg of 2-mercaptopropionylglycine (2-MPG)/kg of body weight orally once daily in increasing doses for 3 weeks. A third dog was given 10 mg of 2-MPG/kg of body weight, IV. The drug was well tolerated. After these initial studies, 15 cystinuric dogs were treated with 2-MPG orally once daily for 5 to 45 months and with sodium bicarbonate for urine alkalinization and fluid diuresis. Pharmacokinetic studies were done in 7 dogs on the third day of oral treatment with 2-MPG. After oral administration of 15.6 to 31.3 of 2-MPG/kg of body weight, maximal serum/plasma concentrations were from 28.6 to 76.3/mumol/L after 1 to 3 hours in 6 cystinuric dogs. The mean urinary excretion was 22% (range, 0.3 to 58.9%) of the dose. Ten of 15 cystinuric dogs had no re-formation of uroliths. Of 4 dogs with uroliths at the beginning of treatment, 3 had total urolith dissolution on continuous treatment. During treatment, further growth of the uroliths was inhibited in one dog, and in another dog with re-formed uroliths, they dissolved. We concluded that 2-MPG is well tolerated and promising for treatment of cystinuric dogs, but the pharmacokinetic studies should be expanded to include different dosage regimens, and results of long-term treatment should be evaluated. Our recommendations for treatment of dogs with cystine uroliths include surgical intervention if the dog has urethral obstruction or has dysuria.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoppe
A
A
Department of Medicine, Swedish University of Agriculture Sciences, Uppsala.
Denneberg
T
T
Kågedal
B
B
D000284:Administration, Oral; D000603:Amino Acids, Sulfur / Q000627:therapeutic use*; D000818:Animals; D003555:Cystinuria / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism; D004285:Dogs; D004361:Drug Tolerance; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D012008:Recurrence; D008625:Tiopronin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014545:Urinary Calculi / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control / Q000662:veterinary*
D000603:Amino Acids, Sulfur; D008625:Tiopronin