Page 166 - Interactive Theoritical Notes of Bioharmaceutics and pharamcokinetics.docx compressed

PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

• For example, probenecid competes with penicillin for the same carrier system

(weak acids).

• So, probenecid competitively inhibits the tubular secretion of the penicillins, and
may be used clinically to prolong the duration of effect of the penicillins.

N.B.:

• For a drug that is excreted solely by glomerular filtration, the elimination half-life

may change markedly in accordance with the binding affinity of the drug for

plasma proteins;

• because the glomeruli restrict the passage of protein-bound drugs.

• In contrast, drug protein binding has very little effect on the elimination half-life

of the drug excreted mostly by active secretion.

• Because the kidney can actively transport some drugs even if the drugs are

protein-bound. (Actually, only free drug is transported, but the protein-drug

complex rapidly dissociates.)

• For example, some of the penicillins are extensively protein bound, but their

elimination half-lives are short due to rapid elimination by active secretion.

• Active secretion occurs primarily in the proximal tubules of the kidney and does

not appear to be influenced by plasma protein binding as discussed.

• The total amount of drug removed from the blood by either glomerular filtration

or active secretion will, if the drug is highly polar, pass into the collecting ducts,

which empty into bladder, and eventually be eliminated from the body in the

urine.

• Kidneys have enormous capacity to reabsorb water from the lumen of these

tubules (only about 1–2mL of the 125mL of the filtrate reaches the bladder).

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