Pharmacokinetics and bioavailability of 2-mercaptopropionylglycine administered intravenously and orally in dogs.
The pharmacokinetic disposition of 2-mercaptopropionylglycine (2-MPG) given as a single intravenous injection and/or as a single oral dose was studied in 9 normal and 13 cystinuric dogs. After intravenous injection of approximately 10 or 20 mg/kg body weight the pharmacokinetics were best described by a three-exponential function. The first phase involved a distribution process apparently including establishment of drug-plasma protein and drug-tissue binding. The second phase involved rapid renal elimination and 60% of the drug was excreted within 3 h of administration. There was also a slow terminal third phase with a long half-life after both intravenous (t1/2 = 23 h) and oral (t1/2 = 22 h) administration. No dose dependency was observed. A deep pool of reversibly tissue-bound 2-MPG was indicated by a Vss of 3.3 +/- 0.9 l/kg body weight and the long terminal elimination phase. Total clearance was estimated as 4.1 +/- 0.9 ml/min/kg body weight. 2-MPG was eliminated mainly by renal excretion, but there was a difference in recovery of dose between normal and cystinuric dogs. During the first 24 h after intravenous and oral administration, 69% and 54%, respectively, of the drug was recovered in the urine of normal dogs. The corresponding figures in cystinuric dogs were 44% and 29%, respectively. The absolute bioavailability (FAUC) was 88 +/- 20% in normal dogs.
Hoppe
A
A
Department of Medicine and Surgery, Swedish University of Agricultural Sciences, Uppsala.
Denneberg
T
T
Emanuelsson
B M
BM
Kågedal
B
B
Lindgren
S
S
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D003555:Cystinuria / Q000378:metabolism / Q000662:veterinary; D004283:Dog Diseases / Q000378:metabolism; D004285:Dogs / Q000378:metabolism*; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D011485:Protein Binding; D008625:Tiopronin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution
D001798:Blood Proteins; D008625:Tiopronin