title: Changes in the use profile of Mectizan: 1987-1997.
abstract: The usually conservative approach of Merck & Co. to drug development became even more so in the Mectizan (ivermectin, MSD) programme because of adverse experiences following 'extra-label' use in Collie dogs and the discovery of a low threshold for acute neurotoxicity in CF-1 mice. Although a very cautious approach and rapid development programme ensued, Merck remained conservative and excluded children under the age of 5 years, pregnant women, and mother who were nursing children under the age of 3 months from treatment. A subsequent, more relaxed set of standards was based on vast human clinical experience, inadvertent use in hundreds of pregnant women without ill-effect, and new laboratory information indicating that the presence of a protective blood-brain barrier protein component (P-glycoprotein) helped to stop Mectizan from crossing the placenta and from crossing the blood-brain barrier in most animal species, including humans. This has allowed more groups to be included in Mectizan treatments: pregnant women living in areas where the risk of loss of sight because of onchocerciasis is very high; and women who are nursing children as young as 1 week of age. Mass distribution of the drug continues to be largely under community control and the likelihood of serious adverse experiences related to finding a human population with unusually low levels of P-glycoprotein (or no P-glycoprotein) seems remote.
authors.affiliation: Worldwide Regulatory Liaison, Biologics/Vaccines, Merck & Co., Inc., West Point, PA 19486-0004, USA. kenneth_brown@merck.com
authors.forename: K R
authors.initials: KR
authors.lastname: Brown
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000818:Animals; D003257:Consumer Product Safety; D000075202:Contraindications; D004285:Dogs; D005260:Female; D005369:Filaricides / Q000600:supply & distribution / Q000627:therapeutic use*; D006801:Humans; D007559:Ivermectin / Q000600:supply & distribution / Q000627:therapeutic use*; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005369:Filaricides; D007559:Ivermectin