The pharmacokinetics of phentermine and chlorphentermine in chronically treated rats

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Abstract
Young rats were treated with [3H]labelled phentermine or chlorphentermine for varying periods (1 day to 8 weeks). The plasma tissue and concentrations of the drugs were determined. The distribution of phentermine reflected a partition, the tissue: blood ratios remaining constant for the entire period. In contrast, chlorphentermine was increasingly accumulated the longer the treatment lasted, as indicated by rising tissue: blood ratios. Chlorphentermine proved to be tightly bound to tissue components. The highest tissue: blood ratio (160 after 8 weeks) was found in lungs and the highest increase in the accumulation rate (10 fold in 8 weeks) was for the adrenals. These results, together with biochemical and ultra-structural findings, suggest that the highly amphiphilic chlorphentermine induces an impairment of phospholipid metabolism resembling lipidosis.

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