Pharmacokinetics and bioavailability of 2‐mercaptopropionylglycine administered intravenously and orally in dogs

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Abstract
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 20mg/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 3h of administration. There was also a slow terminal third phase with a long half‐life after both intravenous (t1‐2=23h) and oral (t1/2=22h) administration. No dose dependency was observed. A deep pool of reversibly tissue‐bound 2‐MPG was indicated by a Vss of 3.3±0.9l/kg body weight and the long terminal elimination phase. Total clearance was estimated as 4.1±0.9ml/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 24h 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.