Hoppe A, Denneberg T, Kågedal B
Department of Medicine, Swedish University of Agriculture Sciences, Uppsala.
Am J Vet Res. 1988 Jun;49(6):923-8.
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)
在一项药代动力学和耐受性研究中,2只健康的比格犬每天口服13.2至39.5毫克/千克体重的2-巯基丙酰甘氨酸(2-MPG),剂量逐渐增加,持续3周。第三只犬静脉注射10毫克/千克体重的2-MPG。该药物耐受性良好。在这些初步研究之后,15只胱氨酸尿症犬每天口服2-MPG一次,持续5至45个月,并服用碳酸氢钠进行尿液碱化和利尿。在口服2-MPG治疗的第三天,对7只犬进行了药代动力学研究。口服15.6至31.3毫克/千克体重的2-MPG后,6只胱氨酸尿症犬在1至3小时后的最大血清/血浆浓度为28.6至76.3微摩尔/升。平均尿排泄量为剂量的22%(范围为0.3%至58.9%)。15只胱氨酸尿症犬中有10只未重新形成尿石。治疗开始时患有尿石的4只犬中,3只在持续治疗后尿石完全溶解。治疗期间,一只犬的尿石进一步生长受到抑制,另一只重新形成尿石的犬的尿石溶解。我们得出结论,2-MPG耐受性良好,有望用于治疗胱氨酸尿症犬,但药代动力学研究应扩大到包括不同的给药方案,并且应评估长期治疗的结果。我们对患有胱氨酸尿石症犬的治疗建议包括,如果犬出现尿道阻塞或排尿困难,则进行手术干预。(摘要截断于250字)