EVALUATION OF SODIUM PYRIDINETHIONE Table Ill. Distribution of asS-labelled material 11 Exposure time (h) Site 4 8 12 16 20 24 Urine 0.49 1.33 2.23 3.88 5.67 6.94 Serum 0.057 0.11 0.14 0.16 0.15 0.16 Liver 0.10 0.15 0.19 0.25 0.22 0.32 Kidney 0.027 0.043 0.043 0.053 0.056 0.10 Lung 0.0052 0.0062 0.0070 0.0071 0.0067 0.014 Heart 0.0025 0.0028 0.0031 0.0046 0.0034 0.0037 Spleen 0.0006 0.0007 0.0006 0.0005 0.0005 0.0006 Brain 0.0014 0.0031 0.0044 0.0080 0.0089 0.0142 Bile 0.0011 0.0021 0.0026 0.0034 0.0041 0.0054 Skeletal muscle/G. 0.0004 0.0003 0.0008 0.0010 0.0009 0.0017 Pancreas/G. 0.0004 0.0006 0.0013 0.0016 0.0012 0.0017 Duodenum/G. 0.0009 0.0006 0.0039 0.0058 0.0059 0.0057 Small intestine/G. 0.0010 0.0009 0.0036 0.0039 0.0054 0.0056 enterohepatic shunt. No significant activity was located in the adrenal glands, gonads, skeletal tissue or adipose tissue. Excretion studies The excretion of asS-labelled material in these six groups of rabbits was mainly via the urine. Fig. 4 shows that the excretion and absorption profiles after 12 h exposure to asS-labelled sodium pyridinethione were linear and parallel, implying that urinary excretion took precedence over tissue con- centration and could be used as a parameter to quantify percutaneous absorption. Fig. 5 revealed that drug serum levels reach a plateau about 12 h. During the initial 12 h exposure period, factors relating to skin penetration and tissue distribution would be expected to influence systemic drug levels, thus explaining the initial rise in serum levels. Thirty rabbits received 0.11 g kg -x of asS-labelled sodium pyridinethione derreally. Five rabbits were killed at 4 h intervals. Tissues were assayed for total activity. Total serum activity was calculated assuming the serum volume was 3•o of the body-weight. The activity was converted to mg equi- valents of drug from the specific activity and expressed as mg kg 4. Mean values were calculated for each group of five rabbits and appear in Table III.

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.