Clinical pharmacokinetics of interferons

Abstract

Interferons are a family of proteins shown to be effective in the treatment of viral (condylomata, acuminata) and neoplastic (hairy cell leukaemia and AIDS-related Kaposi's sarcoma) diseases. To date, the clinical utility of the interferons has been hampered by an incomplete understanding of their mechanism of action. However, there is supporting evidence that the route of administration, i.e. the pharmacokinetic behaviour, is an important treatment variable. The pharmacokinetics of interferons have been fairly well described. The decline in serum concentrations of interferon is rapid after intravenous administration. The volume of distribution approximates 20 to 60% of bodyweight. Work in animals suggests that the catabolism of interferons falls within the natural handling of proteins. Clearance values vary (4.8 to 48 L/h) across the family of interferons and probably reflect the natural internal digestion and turnover of these proteins. Terminal elimination half-lives range from 4 to 16 hours, 1 to 2 hours and 25 to 35 minutes for alpha, beta and gamma, respectively. Intramuscular and subcutaneous administration of interferons alpha and beta results in protracted but fairly good absorption: greater than 80% for interferon-alpha and 30 to 70% for interferon-gamma. Interferon therapy is associated with adverse events which are usually mild and reversible. Temporal relationships exist between the degree and duration of adverse effects and the route of administration. Attempts to relate inducible biochemical markers, such as 2',5'-oligoadenylate synthetase activity, to dose or concentration have met with some success although alterations in these markers have not been shown to relate to clinical response.(ABSTRACT TRUNCATED AT 250 WORDS)