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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1993 Jan;35(1):20–29.

The concentration-dependent disposition of intravenous p-aminohippurate in subjects with normal and impaired renal function.

L F Prescott 1, S Freestone 1, J A McAuslane 1
PMCID: PMC1381485  PMID: 8448064

Abstract

1. The disposition and kinetics of p-aminohippuric acid (PAH) were studied in 27 healthy male volunteers, 10 healthy female volunteers and 10 patients with chronic renal impairment following rapid intravenous injection of 10 mg kg-1. In addition, the renal clearances of PAH and its metabolite N-acetyl-PAH were measured in 10 of the healthy male volunteers following conventional administration of PAH by loading dose and constant infusion, and in another eight during sequential 'step-up' and 'step-down' infusions intended to maintain low, medium and high plasma concentrations below the threshold for onset of saturation of tubular transport. 2. PAH was eliminated rapidly with a mean half-life of less than 30 min in the healthy volunteers and 72 min in the renal patients. The corresponding estimates for acetyl-PAH were 49 and 153 min. In both groups the rate of disappearance of PAH slowed progressively over the period of observation and there was no true log-linear terminal elimination phase. 3. In the healthy volunteers about 50% of the dose was excreted in the urine in 30 min with quantitative recovery in 3 h. In 8 h, 17% of the dose was recovered as acetyl-PAH. In the patients with renal impairment the 8 h recovery was only 83.6% of the dose with 26.9% of the total appearing as acetyl-PAH. 4. The volume of distribution (Vss) of PAH was 16-18 l in the healthy subjects and renal patients. Acetyl-PAH appeared to have a much larger distribution volume (mean 65.5 l in the healthy volunteers). 5. In the healthy volunteers the renal clearance of PAH fell dramatically from 599 +/- 115 ml min-1 1.73m-2 during the first hour after administration to 300 +/- 208 ml min-1 1.73 m-2 during the second hour (P < 0.001). The corresponding renal clearances of acetyl-PAH were 775 +/- 196 and 916 +/- 212 ml min-1 1.73 m-2. In the patients with renal impairment the renal clearance of PAH fell from 194 +/- 83 ml min-1 1.73 m-2 in the first hour to only 61 +/- 19 ml min-1 1.73 m-2 from 4 to 6 h. Over the same period there was no significant fall in the clearances of acetyl-PAH or total PAH (acetyl-PAH + PAH).(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BLOCK J. B., BURROWS B. A. Influence of serum protein binding on renal clearance of I 131-labeled diodrast. J Lab Clin Med. 1960 Sep;56:463–472. [PubMed] [Google Scholar]
  2. Berger E. Y., Farber S. J., Earle D. P., Jackenthal R. COMPARISON OF THE CONSTANT INFUSION AND URINE COLLECTION TECHNIQUES FOR THE MEASUREMENT OF RENAL FUNCTION. J Clin Invest. 1948 Nov;27(6):710–716. doi: 10.1172/JCI102020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brun C., Hilden T., Raaschou F. THE SIGNIFICANCE OF THE DIFFERENCE IN SYSTEMIC ARTERIAL AND VENOUS PLASMA CONCENTRATIONS IN RENAL CLEARANCE METHODS. J Clin Invest. 1949 Jan;28(1):144–152. doi: 10.1172/JCI102043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CONN R. B., SABO A. J., LANDES D., HO J. Y. INCONSTANCY OF RENAL CLEARANCE VALUES WITH CHANGING PLASMA CONCENTRATIONS. Nature. 1964 Jul 11;203:143–146. doi: 10.1038/203143a0. [DOI] [PubMed] [Google Scholar]
  5. Carpenter H. M., Mudge G. H. Uptake and acetylation of p-aminohippurate by slices of mouse kidney cortex. J Pharmacol Exp Ther. 1980 May;213(2):350–354. [PubMed] [Google Scholar]
  6. Chasis H., Redish J., Goldring W., Ranges H. A., Smith H. W. THE USE OF SODIUM p-AMINOHIPPURATE FOR THE FUNCTIONAL EVALUATION OF THE HUMAN KIDNEY. J Clin Invest. 1945 Jul;24(4):583–588. doi: 10.1172/JCI101639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cole B. R., Giangiacomo J., Ingelfinger J. R., Robson A. M. Measurement of renal function without urine collection. A critical evaluation of the constant-infusion technic for determination of inulin and para-aminohippurate. N Engl J Med. 1972 Nov 30;287(22):1109–1114. doi: 10.1056/NEJM197211302872202. [DOI] [PubMed] [Google Scholar]
  8. ELWOOD C. M., ARMENIA J., ORMAN D., MORRIS A., SIGMAN E. M. MEASUREMENT OF RENAL PLASMA FLOW BY IODOPYRACET I-131. JAMA. 1965 Sep 6;193:771–774. doi: 10.1001/jama.1965.03090100017004. [DOI] [PubMed] [Google Scholar]
  9. Frindt G., Vial S. Conjugation of para-aminohippuric acid by human kidney and liver slices. Acta Physiol Lat Am. 1968;18(1):47–54. [PubMed] [Google Scholar]
  10. Girndt J., Mályusz M., Rumpf K. W., Neubaur J., Scheler F. Metabolism of p-aminohippurate and its relevance in man. Nephron. 1974;13(2):138–144. doi: 10.1159/000180386. [DOI] [PubMed] [Google Scholar]
  11. Reidenberg M. M. Kidney disease and drug metabolism. Med Clin North Am. 1974 Sep;58(5):1059–1062. doi: 10.1016/s0025-7125(16)32101-0. [DOI] [PubMed] [Google Scholar]
  12. SETCHELL B. P., BLANCH E. Conjugation of p-aminohippurate by the kidney and effective renal plasma-flow. Nature. 1961 Jan 21;189:230–231. doi: 10.1038/189230b0. [DOI] [PubMed] [Google Scholar]
  13. Smith H. W., Finkelstein N., Aliminosa L., Crawford B., Graber M. THE RENAL CLEARANCES OF SUBSTITUTED HIPPURIC ACID DERIVATIVES AND OTHER AROMATIC ACIDS IN DOG AND MAN. J Clin Invest. 1945 May;24(3):388–404. doi: 10.1172/JCI101618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. TACKET H. S., HOUCK C. R. Measurement of renal hemodynamics in man by the "slope method" without urinalysis. Proc Soc Exp Biol Med. 1950 Jun;74(2):317–321. doi: 10.3181/00379727-74-17890. [DOI] [PubMed] [Google Scholar]
  15. TAGGART J. V. Protein binding of p-aminohippurate in human and dog plasma. Am J Physiol. 1951 Oct;167(1):248–254. doi: 10.1152/ajplegacy.1951.167.1.248. [DOI] [PubMed] [Google Scholar]
  16. Vögeli B., Riedwyl H., Donath A., Oetliker O. Comparison of glomerular filtration rate and effective renal plasma flow determinations obtained by a single injection technique and by means of a standard clearance technique in children. Acta Paediatr Scand. 1971 Sep;60(5):528–532. doi: 10.1111/j.1651-2227.1971.tb06985.x. [DOI] [PubMed] [Google Scholar]

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