PHARMACOKINETICS AND RESISTANCE OF PENICILLINS

PHARMACOKINETICS OF PENICILLINS:

(1) ADMINISTRATION:

The route of administration is determined by the stability of drug to gastric acid and by the severity of infection.

(a) ROUTES OF ADMINISTRATION:

Ticarcillin, carbenicillin and piperacillin and the combinations of ampicillin with sulbactam, ticarcillin and clavulanic acid and piperacillin with tazobactam must be administered intravenously or intramuscularly.

INTRAVENOUS ADMINISTRATION

INTRAMUSCULAR ADMINISTRATION

Penicillin V, amoxicillin and carbenicillin are only available as oral preparations.

ORAL ADMINISTRATION

(b) Depot forms:

Procaine Penicillin G and benzathine Penicillin G are administered intramuscularly and serve as depot forms. They are slowly absorbed into the circulation.

(2) ABSORPTION:

Most of the penicillins are incompletely absorbed after oral adminstration and they reach the intestine in sufficient amounts to affect the compsition of intestinal flora. However, amoxicillin is completely absorbed. Absorption of all the penicillinase- resistant penicillins is decreased by food in the stomach, because gastric emptying time is lengthened and the drugs are destroyed in an acidic environment. Therefore, they must be administered thirty to sixty minutes before meals. Other penicillins are less affected by food.

(3) DISTRIBUTION:

All penicillins cross the placental barrier but none has been shown to be teratogenic. However, peneteration into bone and cerbebrospinal fluid is insufficient for therapy unless these sites are inflammed. However, distribution through out the body is good.

(4) METABOLISM:

Metabolism of penicillins is insignificant, but metabolism of Penicillin G has been shown to occur in patients with impaired renal function.

(5) EXCRETION:

The primary route of excretion is tubular secretory systemof kidney as well as by glomerular filtration. Nafcillin is eliminated primarily through biliary route. Penicillins are also excreted into breast milk and into saliva.

GLOMERULAR FILTRATION

RESISTANCE OF PENICILLINS:

Natural resistance to penicillins occur in organisms that either lack a peptidoglycan cell wall or have cell walls that are impermeable to the drugs. Acquired resistance to the penicillins by plasmid transfer has become a significant clinical problem because an organism may become resistant to several antibiotics at the same time due to the acqiurement of plasmid that encodes resistance to multiple agents. Multiplication of such an organism will lead to increased dissemination of resistance genes. By obtaining a resistance plasmid, bacteria may acquire one or more of the following properties:

(1) Beta lactamase activity.

(2) Decreased permeability to the drug.

(3) Altered Penicillin binding Proteins.