Toxicology

Paracetamol (acetaminophen) is a widely available over-the-counter analgesic antipyretic. It has a long history of use in the general public, however, it has a number of classical toxicities associated with it. It is loosely classified as a non-steroidal anti-inflammatory drug (NSAID). You have been asked by management to compare a potential topical preparation of Paracetamol (acetaminophen) with one containing diclofenac. The objectives are to • Compare potential toxicities particularly considering topical administration o Both are known oral products; how might topical administration affect toxicity? • To indicate if any new testing of the proposed paracetamol product might be needed – or to say why it is not needed • Are there any potential non-clinical or clinical issues or problems that may be associated with this project? • To make a recommendation as to whether to develop a topical formulation of paracetamol. This should follow this contents list; comment may be brief but you need to show that you have considered each point. 1. INTRODUCTION 2. METHODS 3. PHARMACOLOGY – brief comparative summary 4. PHARMACOKINETICS 5. TOXICOLOGY 5.1 Single-dose toxicity 5.2 Repeat-dose toxicity 5.3 Genotoxicity 5.4 Carcinogenicity 5.5 Reproductive and Developmental toxicity 5.6 Local Tolerance / Other toxicity studies (what do you expect here?) 6. CLINICAL EXPERIENCE (just a summary, including clinical dosage) 7. DISCUSSION & RECOMMENDATION 8. REFERENCES