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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.

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