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 TmPAH, 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 Smith1; Wesson2; Bauer3; Pitts4; and Schnurr5. 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 = UPAHV/ PPAH Where UPAH = concentration of PAH (mg/mL) in the urine
V = rate of urine excretion (mL/min), and
PPAH = plasma concentration of PAH (mg/mL). Example: UPAH = 8.0 mg/mL V = 1.5 mL/min PPAH = 0.02 mg/mL ERPF = 8.0 x 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 (TmPAH) Mechanism The quantity of PAH secreted by the tubules (TmPAH) is given by the difference between the total rate of excretion (UPAHV) and the quantity filtered by the glomeruli (GFR x PPAH). Hence: TmPAH= UPAHV – (GFR x PPAH x 0.83) The factor, 0.83, corrects for that portion of PAH which is bound to plasma protein and hence is unfilterable. Example: UPAH = 9.55 mg/mL
V = 16.68 mL/min
GFR = 120 mL/min
PPAH = 0.60 mg/mL
Then TmPAH = 9.55 x 16.68 – (120 x 0.60 x 0.83) = 100 mg/min. Average normal values of TmPAH are 80-90 mg/min. The value of the expression UPAHV, used in calculations of ERPF and TmPAH, 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 m2. Corrections for variations in surface area are made by multiplying the values obtained for ERPF and TmPAH by 1.73/A, where A is the subject surface area. REFERENCES 1. Smith, H.W.: Lectures on the kidney, University Extension Division, University of Kansas, Lawrence, Kansas, 1943. 2. Wesson, L.G., Jr.: "Physiology of the Human Kidney," New York, Grune & Stratton, 1969, pp. 632-655. 3. Bauer, J.D.; Ackermann, P.G.; Toro, G.: "Brays Clinical Laboratory Methods," ed. 7, St. Louis, Mosby, 1968. 4. Pitts, R.F.: "Physiology of the Kidney and Body Fluids," ed. 2, Chicago, Year Book Medical Publishers, 1968. 5. Schnurr, E.; Lahme, W.; Kuppers, H.: Measurement of renal clearance of inulin and PAH in the steady state without urine collection; Clinical Nephrology, 13(1): (26-29), 1980.