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The renal excretory mechanism of an orally active inhibitor of angiotensin converting enzyme (SA-446) was examined in anesthetized dogs. Parenteral administration of this compound resulted in production of constant levels of about 2 mg/l in the plasma (PSA) and the urine concentration was 726 +/- 200 mg/l, a level significantly higher than that in the plasma. Renal clearance of SA-446 (CSA) was 2.24 +/- 0.34 ml/g X min and was significantly higher than GFR. The clearance ratio (CSA/GFR) of over 1.0 was indicative of a net tubular secretion. Administration of probenecid resulted in a significant rise in PSA and in a significant decrease in urinary excretion but with no change in the plasma protein binding ratio. CSA decreased significantly from 2.24 +/- 0.34 to 0.71 +/- 0.14 ml/g X min. The inhibitory action of SA-446 (0.02 mg/kg, i.v.) on the pressor response to angiotensin I disappeared at about 50 min, this action being maintained for about 2 h in the probenecid pretreated dog. Since probenecid is a competitive inhibitor of organic anion secretory transport, our results show the net tubular secretion of SA-446, via organic anion transport systems. Prolongation of the action of SA-446, as induced by probenecid may be due to the increase of plasma concentration, by the inhibition of tubular secretion.
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
June 1985,
Japanese journal of pharmacology,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
January 1988,
Archives internationales de pharmacodynamie et de therapie,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
November 1985,
Nihon Jinzo Gakkai shi,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
December 1986,
Japanese journal of pharmacology,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
January 1987,
Cardiovascular drugs and therapy,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
December 1993,
American journal of kidney diseases : the official journal of the National Kidney Foundation,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
January 1984,
Clinical and experimental hypertension. Part A, Theory and practice,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
November 1989,
Bulletin of the Osaka Medical College,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
December 2005,
Journal of veterinary pharmacology and therapeutics,
Y Abe, and
T Okahara, and
K Miura, and
T Yukimura, and
T Takada, and
T Iwatani, and
T Iso, and
K Yamamoto
July 1982,
The Journal of pharmacology and experimental therapeutics,
