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Pharmacokinetics of the Penicillins in Man

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Summary

The purpose of this article is to review and summarise those aspects of the pharmacokinetic behaviour of the penicillins that may be of particular interest to the clinician.

While these antibiotics differ markedly in their acid stability and oral absorption, misleading inferences may be drawn from simple inspection of the maximal serum concentrations produced by a given dose administered orally. A more accurate picture emerges when serum protein binding and intrinsic activity of the drugs are taken into account. All of the penicillins are readily and actively secreted by the renal tubules and most are eliminated, almost completely unchanged, in the urine. The majority are excreted in small quantities in the bile, but this is a major route for elimination of nafcillin from the body.

Distribution of the penicillins in ‘non-specialised’ sites is excellent. In contrast, penetration of the central nervous system and eye are poor, and of the prostate, minimal. Inflammation reduces the barriers to penetration of these areas. However, quantitative data related to this phenomenon in man are few. Probenecid actively competes with the ‘export’ pump of the meninges and renal tubular cells. This results in an increase in concentrations of the penicillins in the blood and cerebrospinal fluid. The effect of this agent on active secretion of these antibiotics from the eye and biliary tract is minimal.

While elimination of the penicillins from the body takes place largely via renal excretion, penicillin V and oxacillin are extensively degraded as well. In contrast to the situation with respect to ‘natural’ and ‘broad-spectrum’ penicillins, the serum half-life of the isoxazolyl congeners and nafcillin is only minimally prolonged in the presence of renal failure. These agents are only weakly haemodialyzable, while the other penicillins are rapidly removed from the circulation by this procedure.

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  1. Infectious Disease Service of the New England Medical Center Hospital and the Infectious Diseases Division of the Department of Medicine of the Peter Bent Brigham Hospital, Peter Bent Brigham Hospital, 721 Huntington Avenue, Boston, Massachusetts, 02115, USA

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Barza, M., Weinstein, L. Pharmacokinetics of the Penicillins in Man. Clin Pharmacokinet 1, 297–308 (1976). https://doi.org/10.2165/00003088-197601040-00004

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