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Pharmacology Solved 2

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Penicillin Pharmacokinetics Calculations

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Penicillin G (Benzylpenicillin) is an example of a weak acid. It has a pKa of 2.8. About 60% of Penicillin G
is bound to plasma proteins. The pharmacokinetic calculations below are based on a urine pH of 5.8, a
plasma drug concentration of 3μg/mL, a glomerular filtration rate of 100 mL/min, and a measured drug
excretion rate of 1200 μg/min.

i.Calculate the free drug plasma concentration

ii. Calculate the drug filtration rate

iii. Calculate the drug reabsorption rate

iv. Calculate the drug secretion rate

v. Calculate the drug excretion rate

vi. Calculate the renal clearance

i. To calculate the free drug plasma concentration, we need to use the Henderson-Hasselbalch equation:

pH = pKa + log([A-]/[HA])

where pH is the urine pH, pKa is the dissociation constant of the drug, [A-] is the concentration of the
drug in its ionized form, and [HA] is the concentration of the drug in its non-ionized form (i.e. the free
drug).

Solving for [HA], we get:

[HA] = [A-] × 10^(pH - pKa)

Given that the urine pH is 5.8 and the pKa of Penicillin G is 2.8, we can calculate:

[HA] = [A-] × 10^(5.8 - 2.8) = [A-] × 1000

Since the total plasma concentration of Penicillin G is 3 μg/mL, and 60% of it is bound to plasma
proteins, the free drug concentration can be calculated as:

Free drug concentration = (0.4) × (3 μg/mL) = 1.2 μg/mL

Therefore, the free drug plasma concentration is 1.2 μg/mL.

ii. The drug filtration rate can be calculated using the formula:
Filtration rate = GFR × free drug concentration

where GFR is the glomerular filtration rate. Plugging in the values, we get:

Filtration rate = (100 mL/min) × (1.2 μg/mL) = 120 μg/min

Therefore, the drug filtration rate is 120 μg/min.

iii. The drug reabsorption rate can be calculated as the difference between the drug filtered at the
glomerulus and the drug excreted in the urine:

Reabsorption rate = Filtration rate - Excretion rate

Plugging in the values, we get:

Reabsorption rate = 120 μg/min - 1200 μg/min = -1080 μg/min

The negative sign indicates that Penicillin G is being reabsorbed from the renal tubules back into the
bloodstream.

iv. The drug secretion rate can be calculated as the difference between the drug excreted in the urine
and the amount of drug that would be excreted if there was no tubular secretion:

Secretion rate = Excretion rate - (GFR × plasma drug concentration)

Plugging in the values, we get:

Secretion rate = 1200 μg/min - (100 mL/min × 3 μg/mL) = 900 μg/min

Therefore, the drug secretion rate is 900 μg/min.

v. The drug excretion rate is given as 1200 μg/min.

vi. The renal clearance can be calculated using the formula:

Renal clearance = Excretion rate / Plasma drug concentration

Plugging in the values, we get:

Renal clearance = 1200 μg/min / 3 μg/mL = 400 mL/min

Therefore, the renal clearance of Penicillin G is 400 mL/min.

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