VA Class:DX101

AHFS Class:

• Kidney Function 36:40

Generic Name(s):

• Aminohippurate Sodium

Aminohippurate sodium (PAH), the sodium salt of the p -amino analog of hippuric acid, is used to estimate effective renal plasma flow.

Aminohippurate sodium (PAH) is used in plasma concentrations of 10-20 mcg/mL to estimate effective renal plasma flow (ERPF) which is an index of renal function. In these low plasma concentrations, PAH is extracted almost completely from the plasma with each passage through functional renal tissue, and the value obtained for PAH clearance is accepted as being numerically equal to the ERPF. In plasma concentrations of 400-600 mcg/mL, PAH is used in conjunction with glomerular filtration rate (GFR) measurements to estimate the functional capacity of the renal tubular secretory mechanism. Since PAH is excreted both by tubular secretion and glomerular filtration, tubular transport capacity can be determined by comparing PAH excretion with values for GFR obtained by inulin clearance. Although this test may be the best quantitative measure of functioning nephron mass, its complexity prevents its widespread use. PAH clearance tests are more accurate but also more complex than phenolsulfonphthalein excretion tests for evaluation of renal blood flow. In most clinical situations, simpler (although less precise) methods of renal function evaluation are used.

Aminohippurate sodium (PAH) is administered only by IV infusion.

Specialized references should be consulted for PAH analysis procedures. For the measurement of ERPF, the plasma concentration of PAH is maintained at 20 mcg/mL, which generally can be achieved with an IV loading dose of 6-10 mg/kg and a maintenance IV infusion at a rate of 10-24 mg/minute. PAH clearance (and ERPF) is determined by simultaneously measuring plasma PAH concentrations and the quantity of PAH excreted in a given time and calculating the ratio of the amount of PAH excreted to the plasma PAH concentration. ERPF may be calculated using the formula:

ERPF = (U × V) / P

where U is the urinary concentration of PAH in mg/mL, V is the rate of urine excretion in mL/minute, and P is the plasma concentration of PAH in mg/mL. Normal values for ERPF based on PAH clearance studies, corrected to a standard 1.73 m² of body surface area, are 675 ± 150 mL/minute for men and 595 ± 125 mL/minute for women.

For the measurement of maximum tubular secretory capacity (T_m), a plasma concentration of PAH sufficient to saturate the capacity of the tubular secretory cells, usually 400-600 mcg/mL, is necessary. Maximum tubular secretory capacity may be calculated using the formula:

T_m = U × V - (GFR × P × 0.83)

where U is the urinary concentration of PAH in mg/mL, V is the rate of urine excretion in mL/minute, GFR is the glomerular filtration rate in mL/minute (determined by inulin clearance), P is the plasma concentration of PAH in mg/mL, and 0.83 represents a correction factor to account for that portion of PAH which is bound to plasma protein and is unfilterable. Average normal values of T_m, corrected to a standard 1.73 m², are 80-90 mg/minute.

The value of the expression U × V used in both formulas may be found by determining the amount of PAH in a measured volume of urine excreted within a specific time period.

Adverse Effects

Adverse reactions which have been reported in association with the administration of aminohippurate sodium (PAH) include nausea, vomiting, cramps, vasomotor disturbances, flushing, tingling, a sensation of warmth, and the desire to defecate or urinate during or shortly after administration of the drug.

Precautions and Contraindications

PAH must be administered with caution in patients with low cardiac reserve, since a rapid increase in plasma volume may precipitate congestive heart failure. The large doses required to achieve the plasma concentrations necessary for the determination of the maximum tubular secretion should be administered slowly and with caution, and the patient should be continuously observed for any adverse reactions. PAH is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.

Patients receiving drugs that employ the same tubular excretory mechanism as PAH may exhibit mutually decreased excretion of the drugs because of competitive inhibition. Agents that share a common excretory mechanism include diuretics, iodopyracet, penicillin, phenolsulfonphthalein, probenecid, and salicylates.

Agents that interfere with colorimetric analytical procedures, including procaine (no longer commercially available in the US), sulfonamides, and thiazolesulfone, prevent accurate urinary measurements of PAH.

Laboratory Test Interferences

PAH may cause falsely increased concentrations of urinary protein in in vitro tests utilizing the Lowry method. PAH may also interfere with laboratory tests based on colorimetric reactions, producing falsely elevated serum concentrations of creatinine and sulfonamides.

Pharmacology

The use of aminohippurate sodium (PAH) is based on its elimination from the body.

Pharmacokinetics

Following IV administration, PAH is distributed mainly throughout the extracellular space. PAH is conjugated and rapidly excreted by the kidneys. The drug is excreted mainly by proximal tubular secretion, but some glomerular filtration also occurs. The biologic half-life of PAH in patients with normal renal function is 24 minutes. At plasma concentrations of 10-20 mcg/mL in patients with normal renal function, approximately 90% of PAH is extracted from the renal circulation during one passage through the kidneys, producing PAH urinary concentrations of 4-8 mg/mL. The relatively high renal clearance rate of PAH may be related to its low degree of protein binding. At plasma concentrations of 400-600 mcg/mL, the maximum capacity of the proximal tubule cells to secrete PAH is reached. Conditions that impair renal circulation and depress the early excretion of PAH include cardiac failure, primary vascular disease, and most primary renal diseases.

Chemistry and Stability

Chemistry

Aminohippurate sodium (PAH) is the sodium salt of the p -amino analog of hippuric acid. Aminohippurate sodium is soluble in water and has a pK_a of 3.83. Aminohippurate sodium injection is a sterile solution of aminohippuric acid in water for injection prepared with the aid of sodium hydroxide and has a pH of 6.7-7.6.

Stability

Solutions of aminohippurate sodium are sensitive to light. Exposure of the injection to temperatures colder than -20°C or warmer than 40°C should be avoided. Changes in color of aminohippurate sodium injection ranging from colorless to yellow-brown do not affect efficacy of the drug.