RESUMEN
WHAT IS KNOWN AND OBJECTIVE: OATP1B1 mediates the transport of a diverse range of amphiphilic organic compounds that include bile acids, steroid conjugates and hormones. This retrospective pharmacogenetic study was conducted to assess the impact of the OATP1B1 c.521T>C single nucleotide polymorphism (SNP) on the pharmacokinetics of the steroidal aromatase inhibitor drug exemestane in healthy volunteers. METHODS: Exemestane (25 mg) was administered orally to 14 healthy post-menopausal women. All of the 14 subjects were sampled for pharmacokinetic (PK) analyses and retrospectively genotyped for OATP1B1 c.521T>C (rs 4149056). RESULTS AND DISCUSSION: Of the 14 subjects enrolled in the study, five were carriers of the minor C allele (OATP1B1 c.521TC+CC) and the remaining nine were carriers of the OATP1B1 c.521TT genotype. PK was assessed over 8 hours post-dosing. Our results showed statistically significant differences (P=.04) in the plasma exemestane AUC0-8 between the OATP1B1 genotype groups. Our data also showed statistically significant differences (P=.04) in the plasma AUC0-8 of 17-hydroexemestane (the major biologically active metabolite) between the OATP1B1 genotype groups. WHAT IS NEW AND CONCLUSION: Our data suggest that the OAPTP1B1 c.521T>C SNP may influence exemestane pharmacokinetics in humans.
Asunto(s)
Androstadienos/farmacocinética , Inhibidores de la Aromatasa/farmacocinética , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Posmenopausia , Administración Oral , Adulto , Androstadienos/administración & dosificación , Área Bajo la Curva , Inhibidores de la Aromatasa/administración & dosificación , Femenino , Genotipo , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado/metabolismo , Persona de Mediana Edad , Farmacogenética , Polimorfismo de Nucleótido Simple , Estudios RetrospectivosRESUMEN
Monoclonal antibody UJ13A radiolabelled with isotopes of iodine has been shown to selectively localize to human neuroblastoma xenografts. When 131I-UJ13A conjugates were given to nude mice at high doses (100-150 microCi), tumours temporarily disappeared, only to regrow. No selection for neuroblastoma cells that were UJ13A - negative was observed. Distribution studies on mice receiving radiolabelled UJ13A demonstrated the antibody is rapidly lost from the blood of animals. This cannot be accounted for by selective uptake into xenografts or any other mouse organ examined. We concluded there is a rapid equilibration of isotope between intra- and extravascular spaces in the animal. The rapid, biphasic loss of UJ13A from the blood of mice may explain why so little injected antibody can target to the human tumour xenografts.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Neuroblastoma/terapia , Animales , Anticuerpos Monoclonales/metabolismo , Cromatografía en Gel , Humanos , Inyecciones Intravenosas , Marcaje Isotópico , Riñón/metabolismo , Cinética , Hígado/metabolismo , Ratones , Ratones Desnudos , Bazo/metabolismoRESUMEN
Hooded Lister rats were found to exhibit symptoms of Mycoplasma pulmonis infection. During the course of this chronic respiratory disease they developed ophthalmia and conjunctivitis which proved to be an opportunist infection with Pasteurella multocida. The severity of disease varied in individual rats, newborn rats entirely escaping infection. All cases responded to treatment with appropriate topical antibiotic and no sequelae were observed.
