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Penicillin G (benzylpenicillin) is an acid-labile compound having variable bioavailability after oral administration. Consequently, penicillin G is most appropriate for intramuscular or intravenous therapy. The drug distributes to most tissues and serosa-lined cavities, although low concentrations appear in breast milk and cerebrospinal fluid. When the meninges are inflamed, cerebrospinal fluid concentrations of penicillin G approximate 5% of the serum concentration. In inflamed joints, concentrations of the drug approach serum levels.

Penicillin G is excreted by the kidneys, with 90% of renal elimination occurring via tubular secretion and 10% by glomerular filtration. Probenecid blocks tubular secretion and has been used to increase the serum concentration and prolong the half-life of penicillin G and other penicillins. Additional pharmacokinetic information can be found in Table 45.1.

The clinical uses of penicillin G include endocarditis caused by S. viridans (or Streptococcus bovis), pharyngitis (group A ß-hemolytic streptococci), cat bite cellulitis (Pasteurella multocida), and syphilis (Treponema pallidum).

Depot intramuscular formulations of penicillin G, including procaine penicillin and benzathine penicillin, have decreased solubility, delayed absorption, and a prolonged half-life. Drug concentrations are detectable 24 hours after injection of procaine penicillin, and low levels of benzathine penicillin (0.003 units/mL) are detectable 4 weeks after injection.

When prescribing one of the penicillin G depot formulations, practitioners must individualize treatment to clinical and microbial conditions. Some long-acting formulations may not maintain adequate plasma and tissue concentrations to treat specific organisms or infections. For acute streptococcal meningitis, the goal is rapid achievement of high antibiotic concentrations in the cerebrospinal fluid. Consequently, depot formulations are inappropriate for meningitis. Intravenous penicillin G is among the antibiotics of first choice for therapy of meningitis caused by susceptible S. pneumoniae. In contrast, a depot formulation of benzathine penicillin G suffices for rheumatic fever prophylaxis.

Penicillin V is an orally administered phenoxy-methyl congener of penicillin G having an antibacterial spectrum of activity that is similar to that of penicillin G. Penicillin V is used to treat streptococcal infections when oral therapy is appropriate and desirable.

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