title: Justification for routine screening of pharmaceutical products in immune function tests: a review of the recommendations of Putman et al. (2003).
abstract: In a recent publication by Putman et al. (2003), salmeterol, morphine/methadone and buprenorphine were quoted as examples of pharmaceutical drugs whose immunotoxicity has only been revealed by conduct of specific immune function tests in non-clinical studies. Review of the published non-clinical data for these drugs has shown that there is no clear evidence of immunotoxicity of salmeterol in these studies, and in addition, there are no clinical issues regarding adverse immunological effects of this drug. Of the opioid drugs, only very minor evidence of immunosuppression by morphine, and marginal evidence of slight immunostimulation by buprenorphine were detected in the non-clinical immune function assays performed at high doses. Methadone showed no effects on immune function assays in animals. As some immunomodulation by opioid drugs might have been expected based on the known pharmacological properties of this drug class, the marginal effects, or lack of effects observed in the immune function tests does raise a question about the sensitivity and specificity of the assays to detect clinically relevant changes. This review has suggested that, based on the cited examples, there is no strong case for routine non-clinical immune function testing of all new pharmaceutical products. A more rigorous evaluation of non-clinical immune function tests, and their ability to discriminate between clinically relevant and non-clinically relevant immunosuppression, is needed before definitive regulatory guidance in this area can be finalized.
authors.affiliation: PR BioServices Ltd, Ramsey St Mary's, Huntingdon, Cambs PE26 2SR, UK. pryle@prbio.co.uk
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ryle
mesh_terms: D000318:Adrenergic beta-Agonists / Q000009:adverse effects; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D002047:Buprenorphine / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D017408:Guidelines as Topic; D006801:Humans; D007154:Immune System Diseases / Q000139:chemically induced* / Q000276:immunology; D007109:Immunity / Q000187:drug effects*; D008691:Methadone / Q000009:adverse effects; D009020:Morphine / Q000009:adverse effects; D009294:Narcotics / Q000009:adverse effects; D000068299:Salmeterol Xinafoate
chemical_list: D000318:Adrenergic beta-Agonists; D009294:Narcotics; D002047:Buprenorphine; D000068299:Salmeterol Xinafoate; D009020:Morphine; D000420:Albuterol; D008691:Methadone