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Tuberculosis (TB), caused byMycobacterium tuberculosis(Mtb), remains a leading cause of death with 1.6 million deaths worldwide reported in 2021. Oral pyrazinamide (PZA) is an integral part of anti-TB regimens, but its prolonged use has the potential to drive development of PZA resistantMtb. PZA is converted to the active moiety pyrazinoic acid (POA) by theMtbpyrazinamidase encoded bypncA, and mutations inpncAare associated with the majority of PZA resistance. Conventional oral and parenteral therapies may result in subtherapeutic exposure in the lung, hence direct pulmonary administration of POA may provide an approach to rescue PZA efficacy for treatingpncA-mutant PZA-resistantMtb.The objectives of the current study were to i) develop novel dry powder POA formulations ii) assess their feasibility for pulmonary delivery using physicochemical characterization, iii) evaluate their pharmacokinetics (PK) in the guinea pig model and iv) develop a mechanism based pharmacokinetic model (MBM) usingin vivoPK data to select a formulation providing adequate exposure in epithelial lining fluid (ELF) and lung tissue.We developed three POA formulations for pulmonary delivery and characterized their PK in plasma, ELF, and lung tissue following passive inhalation in guinea pigs. Additionally, the PK of POA following oral, intravenous and intratracheal administration was characterized in guinea pigs. The MBM was used to simultaneously model PK data following administration of POA and its formulations via the different routes. The MBM described POA PK well in plasma, ELF and lung tissue.Physicochemical analyses and MBM predictions suggested that POA maltodextrin was the best among the three formulations and an excellent candidate for further development as it has: (i) the highest ELF-to-plasma exposure ratio (203) and lung tissue-to-plasma exposure ratio (30.4) compared with POA maltodextrin and leucine (75.7/16.2) and POA leucine salt (64.2/19.3); (ii) the highest concentration in ELF (CmacELF: 171 nM) within 15.5 minutes, correlating with a fast transfer into ELF after pulmonary administration (kPM: 22.6 1/h).The data from the guinea pig allowed scaling, using the MBM to a human dose of POA maltodextrin powder demonstrating the potential feasibility of an inhaled product.Table of Contents (TOC)/Abstract Graphic

Supplemental material, sj-docx-2-jiv-10.1177_08862605221141863 for Epidemiological Profile of Intimate Partner Homicides of Sexual and Gender Minority Women in the United States, 2003 to 2017 by Elizabeth J Anderson, Heather Marlow and Chimaraoke Izugbara in Journal of Interpersonal Violence

Supplemental material, sj-docx-2-jiv-10.1177_08862605221141863 for Epidemiological Profile of Intimate Partner Homicides of Sexual and Gender Minority Women in the United States, 2003 to 2017 by Elizabeth J Anderson, Heather Marlow and Chimaraoke Izugbara in Journal of Interpersonal Violence

Supplemental material, sj-docx-1-jiv-10.1177_08862605221141863 for Epidemiological Profile of Intimate Partner Homicides of Sexual and Gender Minority Women in the United States, 2003 to 2017 by Elizabeth J Anderson, Heather Marlow and Chimaraoke Izugbara in Journal of Interpersonal Violence

Supplemental material, sj-docx-1-jiv-10.1177_08862605221141863 for Epidemiological Profile of Intimate Partner Homicides of Sexual and Gender Minority Women in the United States, 2003 to 2017 by Elizabeth J Anderson, Heather Marlow and Chimaraoke Izugbara in Journal of Interpersonal Violence

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My project aims to investigate the medieval\ud concepts of masculinity within the framework of the Angevin royal family, concentrating on the\ud processes involved in the transition from childhood through youth to masculine adulthood of six members of the Angevin royal family over two generations.