Pharmacokinetics/Pharmacodynamics

PK/PD

Absorption can be from the GI tract after oral, rectal, or tube administration. It can also be from IM, subcutaneous, or topical administration.

Bioavailability is the fraction of dose that is absorbed intact. IV antibiotics have 100% bioavailability. Fluroquinolones, flucanazole, cotrimoxazole, nitrofurantoin all have 100% bioavailability.

Apparent volume of distribution reflects the ability of the drug to enter inflammatory cells and tissues.

Rapidly metabolized antibiotics excreted by the kidneys are not a good choice for urinary tract infections.

Drugs with short half lives need more frequent administration. Drugs with longer half lives can be given in a single daily dose and are more convenient. Drugs primarily excreted via the hepatic or biliary system need dose adjustment in renal insufficiency and might accumulate inappropriately in patients with hepatic failure.

Peak/MIC ratio, Cmax/MIC ratio is the ratio of the maximum serum concentration to the MIC. AUC/MIC is the ratio of the area under the concentration-time curve to the MIC. Both predict activity of concentration dependant bactericidal antibiotics.

Concentration-dependant killing agents such as fluroquinolones and aminoglycosides eliminate bacteria when their concentrations are above the MIC of the organism. As the ratio of drug concentration to MIC increases, bacterial killing increases. Cmax/MIC can also be helpful in seeing the development of bacterial resistance for aminoglycosides and quinolones.

t>MIC is the duration of time during the dose interval that serum concentration stays above MIC. This predicts activity of time dependent bactericidal antibiotics. These include β-lactams, macrolides, and clindamycin. Any dosing strategy requires clinical investigations in human studies before they can be used in clinical practice.

Postantibiotic effect (PAE) is growth inhibition that continues for a varying period after the concentration of the antibiotic is below the MIC. Aminoglycosides and fluoroquinones have in vitro PAEs against gram – of about 2-6 hrs. β-lactam antibiotics have little to no PAE against gram-, but 2 hours vs. gram+. There is in vivo PAE against gram - for aminoglycosides, fluorquinolones, erythromycin, clindamycin, and tetracycline. PAE is important cuz theoretically a drug with long PAE can be used less frequently. A drug with no PAE might be most effective if given as a continuous infusion.

Category: Pharmacology Notes