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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cerebral toxicity of penicillins in relation to their hydrophobic character.

The neurotoxic effects of ticarcillin, methicillin, phenthicillin, oxacillin, cloxacillin and dicloxacillin were studied in the conscious rabbit. During and after intravenous administration of 1.2 and 2.4 g/kg, resp., over 50 min the blood concentrations of the drugs were determined and the neurotoxicity assessed by continuous recording of the electroencephalogram. The hydrophobia of the penicillins was characterized by determination of their partition coefficients between isobutanol and buffer solution pH 7. 4. The penicillins showed quite different neurotoxic properties. A close correlation (r = 0.928) was found between the neurotoxic potency of the penicillins and their partition coefficients. With increasing hydrophobia the neurotoxic potency increased in the following sequence: Ticarcillin, methicillin, oxacillin, phenethicillin, cloxacillin, dicloxacillin. It can be concluded, therefore, that determination of the partition coefficient of a penicillin gives valuable information on the neurotoxicity to be expected. The introduction of a neurotoxicity quotient revealed that penicillins may be divided into two groups: less neurotoxic penicillins with a partition coefficient below 1.0 and highly neurotoxic penicillins with a partition coefficient above 1.0.[1]


  1. Cerebral toxicity of penicillins in relation to their hydrophobic character. Weihrauch, T.R., Köhler, H., Höffler, D. Naunyn Schmiedebergs Arch. Pharmacol. (1975) [Pubmed]
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