Aminohippurate sodium \"\"pah\"\" injection

Name: Aminohippurate sodium \"\"pah\"\" injection

Clinical Pharmacology

PAH is filtered by the glomeruli and is actively secreted by the proximal tubules. At low plasma concentrations (1.0 to 2.0 mg/100 mL), an average of 90 percent 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 (Tm PAH ). This is accomplished by elevating the plasma concentration to levels (40-60 mg/100 mL) sufficient to saturate the maximal capacity of the tubular cells to secrete PAH.

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

Indications and Usage

Estimation of effective renal plasma flow.

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

Contraindications

Hypersensitivity to this product or to its components.

Dosage and Administration

For intravenous use only

Clearance measurements using single injection techniques are generally inaccurate, particularly in the measurement of ERPF. For this reason, intravenous 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 per 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 Tm PAH , the plasma level of PAH must be sufficient to saturate the capacity of the tubular secretory cells. Concentrations from 40 to 60 mg per 100 mL are usually necessary.

Technical details of these tests may be found in Smith 1 ; Wesson 2 ; Bauer 3 ; Pitts 4 ; and Schnurr. 5

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:

ERPF = U PAH V
P PAH
Where U PAH = concentration of PAH
(mg/mL) in the urine
V    = rate of urine excretion
(mL/min), and
P PAH = plasma concentration
of PAH (mg/mL).
Example: U PAH = 8.0 mg/mL
V    = 1.5 mL/min
P PAH = 0.02 mg/mL
ERPF = 8.0 × 1.5
0.02
= 600 mL/min

Based on PAH clearance studies, the normal values for ERPF are:

men 675 ± 150 mL/min
women 595 ± 125 mL/min.

Maximum Tubular Secretory

Mechanism (Tm PAH )

The quantity of PAH, secreted by the tubules (Tm PAH ) is given by the difference between the total rate of excretion (U PAH V) and the quantity filtered by the glomeruli (GFR × P PAH ). Hence:

Tm PAH = U PAH V - (GFR × P PAH × 0.83)

The factor, 0.83, corrects for that portion of PAH which is bound to plasma protein and hence is unfilterable.

Example: U PAH = 9.55 mg/mL
V = 16.68 mL/min
GFR = 120 mL/min
P PAH = 0.60 mg/mL

Then Tm PAH = 9.55  ×  16.68 - (120  ×  0.60 ×  0.83) = 100 mg/min.

Average normal values of Tm PAH are 80-90 mg/min.

The value of the expression U PAH V, used in calculations of ERPF and Tm PAH , may be found by determining the amount of PAH in a measured volume of urine excreted within a specific period of time.

These calculations are based on a body surface area of 1.73 m 2 . Corrections for variations in surface area are made by multiplying the values obtained for ERPF and Tm PAH by 1.73/A, where A is the subject surface area.

How Supplied

No. 95--Aminohippurate Sodium, 20 percent sterile solution for intravenous injection, is supplied as follows:

NDC 0006-3395-11 in 10 mL vials.

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

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