12 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 7 g 4 :5 I 9 • x ••'•1 I I ,I I 4 8 12 i 6 20 24 Time (h) Figure 4. Absorption (X)and excretion (¸) rates of sulphur-35 labelled sodium pyridinethione and metabolites over 24 h exposure time. 0 16 u• 0'12 E 008 0'06 0.04 0'02 I I I I I I 4 8 12 16 20 24 Time (hi Figure 5. Serum levels of sulphur-35 labelled sodium pyridinethione and metabolites over 24 h exposure time.

EVALUATION OF SODIUM PYRIDINETHIONE 13 Further evidence that excretion of the drug took place in preference to tissue concentration was gained when the ratio of urine, serum, liver and kidney levels were determined for the six groups of rabbits (Table IV). Table IV. Ratio of a•S-labelled material in urine, serum, liver, kidney Exposure time (h) Location 4 8 12 16 20 24 Urine 8.7 11.7 16.1 24.4 33.1 44.2 Serum 1.0 1.0 1.0 1.0 1.0 1.0 Liver 1.8 1.3 1.4 1.5 1.5 2.0 Kidney 0.5 0.4 0.3 0.3 0.4 0.6 The only amounts changing significantly with extended exposure were the urine levels. Metabolic rate of sodium pyridinethione In accordance with the method outlined, urine and tissues were sub- jected to a chromatographic and spectrophotometric analysis with the aim of identifying the metabolites following percutaneous absorption. Table V records the Rf values for reference compounds and components of urine and tissues with ass activity. Table V shows that the urine and tissues examined contained pyridine-N- oxide 2 sulphonic acid the urine and liver also had detectable levels of Table V. Rf values for reference compounds and components of urine and tissues with a•S activity Reference compounds and materials examined Solvent systems Isobutanol 1' Propanol 4: Ammonia 2 N-Butanol 5: Acetic acid 1: Water 2 Sodium pyridinethione Pyridine-N-oxide 2 sulphonic acid Urine components Tissue components: Liver Kidney Lung Brain Heart 0.42 0.42 0.43 0.25 0.27 0.26 0.26 0.25 0.24 0.26 0.85 0.86 0.86 0.18 0.16 0.17 0.16 0.16 0.16 0.17