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At least 1,171 records · Page 65Linked to original sources
PubMed1989

Renal clearance of substituted hippurates in the dog. I. Benzoylglycine (hippurate) and methyl-substituted benzoylglycines.

Plasma kinetics and renal excretion of benzoylglycine (hippurate) and methyl-substituted benzoylglycines were studied in three Beagle dogs, after rapid i.v. administration of about 1 g of glycine conjugate. Benzoylglycine and the 3- and 4-methyl analogs showed nonlinear plasma protein binding varying between 20 and 80% over a concentration range of 5 to 450 micrograms/ml. For 2-methylbenzoylglycine an extremely high protein binding, practically approaching 100%, was observed at low plasma levels (less than 50 micrograms/ml). All conjugates were cleared largely via the kidney (greater than 80% of the dose) and, except for the 2-methyl analog, eliminated rapidly from plasma. Plasma concentration and renal excretion rate data were analyzed simultaneously with a previously developed physiologically based kidney model. Tubular secretion appeared to be a function of the total drug concentration in renal plasma, except for 2-methylbenzoylglycine, presumably due to its tight protein binding. The average values of the parameters characterizing the tubular transport maximum (TM in milligrams per minute) and the apparent affinity for the secretory system (KT in micrograms per milliliter) were: benzoylglycine TM = 5.5 +/- 0.8, KT = 40 +/- 5; 3-methylbenzoylglycine TM = 7.1 +/- 3.3, KT = 49 +/- 1; 4-methylbenzoylglycine TM = 8.0 +/- 1.6, KT = 14 +/- 6. Secretion of 2-methylbenzoylglycine was not saturated. Accordingly, only the ratio TM/KT = 163 +/- 54 ml/min could be calculated. An interesting observation was the partial deconjugation of 4-methylbenzoylglycine to its corresponding benzoate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Renal clearance of substituted hippurates in the dog. II. 4-Amino-, hydroxy- and methoxy-substituted benzoylglycines.

Plasma kinetics and renal excretion of 4-aminobenzoylglycine (p-aminohippurate), hydroxy- and methoxy-substituted benzoylglycines were studied in three Beagle dogs after rapid i.v. administration of about 1 g. Plasma protein binding of 4-amino-, 3-hydroxy- and 4-hydroxybenzoylglycine was low (less than 15%) and practically constant over a range of 5 to 450 micrograms/ml, whereas the 2-hydroxy analog showed concentration-dependent protein binding (40-80%). The excretory patterns of the 4-amino, 3- and 4-hydroxy analogs were essentially the same; rapid elimination from plasma into urine (greater than 80% of the dose), mainly by very efficient supply-limited tubular secretion. Conversely, the excretion of 2-hydroxybenzoylglycine was characterized by a lower plasma clearance and total renal excretion (64% of the dose), and a limited capacity of the tubular secretory system. The methoxybenzoylglycines showed nonlinear plasma protein binding varying between 10 and 70%, rapid clearance from plasma, largely by renal excretion (72-84% of the administered dose). Tubular secretion of 2- and 3-methoxybenzoylglycine was saturated, whereas complete saturation was not achieved for the 4-methoxy isomer. The kinetic parameters of tubular secretion were estimated with a physiologically based kidney model: 2-hydroxy, tubular transport maximum (TM) = 4.4 +/- 0.9 mg/min, Michael-Menten constant of the tubular secretion mechanism (KT) = 23 +/- 8 micrograms/ml; 2-methoxy-TM = 11.7 +/- 4.9 mg/min, KT = 42 +/- 9 micrograms/ml; 3-methoxy-TM = 8.8 +/- 1.0 mg/mn, KT = 27 +/- 20 micrograms/ml. Inasmuch as secretion of the other compounds was not saturated, only the intrinsic secretion clearance (CLint) = TM/KT could be estimated; 4-amino-CLint = 145 +/- 50 ml/min, 3-hydroxy-CLint = 194 +/- 21 ml/min, 4-hydroxy-CLint = 153 +/- 23 ml/min and 4-methoxy-CLint = 201 +/- 47 ml/min. The 4-methoxy isomer was metabolized to some extent by deconjugation of the glycine moiety and the resulting benzoate was found in plasma but not in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1954

Blood substitutes.

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Blood Substitutes↗