Pharmacokinetics
The oral bioavailability of MGA is approximately 100%. After a single low oral dose of 4 mg MGA, peak serum concentrations of MGA were about 7 ng/dL (18 nmol/L) and occurred after 3 hours. Following a single high oral dose of 160 mg micronized MGA in men, peak circulating levels of MGA were 125 ng/mL (325 nmol/L) and occurred after 6.3 hours. This study found that micronized MGA at this dose showed considerably improved absorption relative to its conventional tablet form. In terms of plasma protein binding, MGA is bound mostly to albumin (82.4%) and is not bound to sex hormone-binding globulin or to corticosteroid-binding globulin. MGA metabolized in the liver mainly by hydroxylation of the C21, C2α, and C6 positions, as well as by reduction and conjugation. Its elimination half-life is 34 hours on average, with a range of 13 to 105 hours. MGA is excreted 57 to 78% in urine and 8 to 30% in feces.At high doses, MGA appears to have far greater bioavailability and potency than medroxyprogesterone acetate, regardless of whether the route of administration of the latter is oral or parenteral. Following oral administration of 80 to 160 mg MGA or 500 to 1,000 mg medroxyprogesterone acetate, circulating levels of MGA were 2- to 10-fold higher than those of medroxyprogesterone acetate. Similar findings have been found for oral MGA relative to medroxyprogesterone acetate administered via intramuscular injection. MGA also reaches steady-state levels more quickly than medroxyprogesterone acetate.
Myeloperoxidase deficiency is a disorder featuring lack in either the quantity or the function of myeloperoxidase–an iron-containing protein expressed primarily in neutrophil granules. There are two types of myeloperoxidase deficiency: primary/inherited and secondary/acquired. Lack of functional myeloperoxidase leads to less efficient killing of intracellular pathogens, particularly Candida albicans, as well as less efficient production and release of neutrophil extracellular traps (NETs) from the neutrophils to trap and kill extracellular pathogens. Despite these characteristics, more than 95% of individuals with myeloperoxidase deficiency experience no symptoms in their lifetime. For those who do experience symptoms, the most common symptom is frequent infections by Candida albicans. Individuals with myeloperoxidase deficiency also experience higher rates of chronic inflammatory conditions. Myeloperoxidase deficiency is diagnosed using flow cytometry or cytochemical stains. There is no treatment for myeloperoxidase deficiency itself. Rather, in the rare cases that individuals experience symptoms, these infections should be treated. Pathophysiology
The innate immune system responds quickly to infection, with neutrophils (a type of white blood cells) being the first responders. Neutrophils enter the site of infection and begin to phagocytose (take up) pathogens. Once engulfed, the neutrophils must then degrade the captured pathogens–a process known as intracellular killing.One method of intracellular killing which takes place in the phagolysosomes of neutrophils involves the reaction of myeloperoxidase with hydrogen peroxide (H2O2) acquired in the cells from NADPH oxidase through the respiratory bursts. This reaction generates several acidic products including hypochlorous acid (HClO), which can break down pathogens.