18-Nov-22

CLINICAL
PHARMACOKINETICS

Maryam Mahmood
Pharm-D, M. Phil (Pharmacy Practice), IPPCR Graduate
Lecturer Clinical Pharmacy
RIPS, City Campus, RIU, Islamabad.

CONCEPT OF ELIMINATION

Drugs may be eliminated from the body by a number of routes. The primary routes are:
1. Excretion of the unchanged drug in the kidneys.
2. Metabolism (usually in the liver) into a more water soluble compound for subsequent
excretion in the kidneys.
3. A combination of both.

Note: The main pharmacokinetic parameter describing elimination is clearance (CL).

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CONTINUED..

1. Clearance (CL) is defined as the volume of plasma completely emptied of drug per unit
time.
2. Rate of Drug Elimination is defined as the amount of drug that leaves the body per unit
time and mathematically it is the multiplicative product of CL and C.
Rate of Drug Elimination = CL × C

FORMULAS

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FORMULAS

FORMULAS

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A. LITHIUM CASE

A 68-year-old Argentinean man (69 kg) was found wandering in the

street. A neighbor alerted the police. He was described as being confused
and agitated. The patient could not speak English and on admission to
hospital could not give a history. The neighbor told the ambulance staff
the patient was normally well, but known to be taking medicines for a
mental disorder. The ambulance staff found lithium and Amisulpride in
the man's pockets. A sample of lithium was taken and reported as 2.5
mmol/L (0.6–1 mmol/L). His plasma creatinine was 160 µmol/L so the
lithium was stopped.

LITHIUM CASE QUESTIONS

1. Calculate the patient's pharmacokinetic parameters clearance (CL),

volume of distribution (Vd), elimination constant (ke) using population
data.
2. Estimate the time for the lithium level to decrease to the middle of the
normal range.
3. Briefly describe the symptoms of lithium toxicity.

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Mnemonic ADRs

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B. THEOPHYLLINE CASE

Mr B is a 38-year old, 63 kg man who suffers from asthma. He has been

admitted to hospital and Nuelin S.A. 500 mg 12 hourly (6 am and 6 pm)
has been added to his regimen. He responds well to this treatment but
unfortunately after 2 days of treatment two doses are missed (evening
dose and following morning dose). The clinical team is anxious to
discharge him, so it is decided to give him a loading dose of
aminophylline at 10 am before restarting him on maintenance therapy.

THEOPHYLLINE CASE QUESTIONS

1. Was the patient at steady state before the medication was omitted?
2. What is the estimated theophylline level at 10 am?
3. The levels were then checked and the theophylline level was reported
as 4 mg/L. What loading dose of i.v. aminophylline would you
recommend?

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C. VANCOMYCIN CASE

A vancomycin solution containing 1000 mg of vancomycin hydrochloride

diluted to 250 mL with D5W is to be infused at a constant rate with a
continuous-drip intravenous infusion set that delivers 25 drops/mL. What
flow rate (drops per minute) should be used to infuse all 250 mL of
the vancomycin hydrochloride solution in 2 hrs?

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D. VANCOMYCIN CASE

A vancomycin solution containing 1000 mg of vancomycin hydrochloride

diluted to 250 mL with D5W is to be infused at a constant rate with an
infusion pump in 2 hrs. What is the rate of drug administration?
(A) 2.08 mg/min
(B) 8.33 mg/min
(C) 4.17 mg/min
(D) 16.70 mg/min
(E) 5.21 mg/min

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REFERENCES

• Comprehensive pharmacy review for NAPLEX / editors, Leon Shargel ... [et
al.]. — 8th ed.
• Clinical Pharmacy and Therapeutics edited by Roger Walker and Cate
Whittlesea

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