Aminohippurate Sodium

AMINOHIPPURATE SODIUM

MSD

Determination of Renal Function

Action And Clinical Pharmacology: Aminohippurate Sodium (PAH) is filtered by the glomeruli and is actively secreted by the proximal tubules. At low plasma concentrations (1 to 2 mg/100 mL), an average of 90% of PAH is cleared by the kidneys from the renal blood stream in a single circulation. It is ideally suited for measurement of ERPF since it has a high clearance, is essentially nontoxic at the plasma concentrations reached with recommended doses, and its analytical determination is relatively simple and accurate.

PAH is also used to measure the functional capacity of the renal tubular secretory mechanism or transport maximum (TmPAH). This is accomplished by elevating the plasma concentration to levels (40 to 60 mg/100 mL) sufficient to saturate the maximal capacity of the tubular cells to secrete PAH.

Inulin clearance is generally measured during TmPAH determinations since glomerular filtration rate (GFR) must be known before calculations of secretory Tm measurements can be done (see Dosage, Calculations).

Indications And Clinical Uses: Estimation of Effective Renal Plasma Flow (ERPF).

Measurement of the functional capacity of the renal tubular secretory mechanism.

Contra-Indications: Hypersensitivity to this product or to its components.

Precautions: General: I.V. solutions must be given with caution to patients with low cardiac reserve, since a rapid increase in plasma volume can precipitate congestive heart failure.

For measurement of ERPF, small doses of PAH are used. However, in research procedures to measure TmPAH, high plasma levels are required to saturate the capacity of the tubular cells. During these procedures the i.v. administration of PAH solutions should be carried out slowly and with caution. The patient should be continuously observed for any adverse reactions.

Children: Safety and effectiveness in children have not been established.

Pregnancy: Animal reproduction studies have not been done with PAH. It is also not known whether PAH can cause fetal harm when given to a pregnant woman or can affect reproduction capacity. PAH should be given to a pregnant woman only if clearly needed.

Lactation: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PAH is administered to a nursing woman.

Drug Interactions: Renal clearance measurements of PAH cannot be made with any significant accuracy in patients receiving sulfonamides, procaine or thiazolesulfone. These compounds interfere with chemical color development essential to the analytical procedures.

Probenecid depresses tubular secretion of certain weak acids such as PAH. Therefore, patients receiving probenecid will have erroneously low ERPF and TmPAH values.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been done to evaluate any effects upon fertility or carcinogenic potential of PAH.

Adverse Reactions: Vasomotor disturbances, flushing, tingling, nausea, vomiting and cramps may occur.

Patients may have a sensation of warmth or the desire to defecate or urinate during or shortly following initiation of infusion.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: The i.v. LD50 in female mice is 7.22 g/kg. tag_DosageDosage

Dosage And Administration: For i.v. use only.

REG>Clearance measurements using single injection techniques are generally inaccurate, particularly in the measurement of ERPF. For this reason, i.v. infusions at fixed rates are used to sustain the plasma PAH concentration at the desired level.

To measure ERPF, the concentration of PAH in the plasma should be maintained at 2 mg/100 mL, which can be achieved with a priming dose of 6 to 10 mg/kg and an infusion dose of 10 to 24 mg/min.

As a research procedure for the measurement of TmPAH, the plasma level of PAH must be sufficient to saturate the capacity of the tubular secretory cells. Concentrations of from 40 to 60 mg/100 mL are usually necessary.

Technical details of these tests may be found in references available from the manufacturer.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use, whenever solution and container permit. Note: The normal color range for this product is a colorless to yellow/brown solution. The efficacy is not affected by color changes within this range.

Calculations: Effective Renal Plasma Flow (ERPF): The clearance of PAH, which is extracted almost completely from the plasma during its passage through the renal circulation, constitutes a measure of ERPF. Hence:

Availability And Storage: Each 10 mL of sterile, nonpreserved aqueous solution for injection, with a pH of 6.7 to 7.6 contains: aminohippurate sodium 2 g (20%), sodium hydroxide to adjust pH and water for injection, q.s. Vials of 10 mL. Avoid storage at temperatures below -20°C and above 40°C. Discard any unused portion.

AMINOHIPPURATE SODIUM MSD Determination of Renal Function

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