Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. Usually both eyes are affected. In more severe cases a scarring or a circle may be seen within the cornea.While the cause is unknown, it is believed to occur due to a combination of genetic, environmental, and hormonal factors. Patients with a parent, sibling, or child who has keratoconus have 15 to 67 times higher risk in developing corneal ectasia compared to patients with no affected relatives. Proposed environmental factors include rubbing the eyes and allergies. The underlying mechanism involves changes of the cornea to a cone shape. Diagnosis is most often by topography. Topography measures the curvature of the cornea and creates a colored "map" of the cornea. Keratoconus causes very distinctive changes in the appearance of these maps, which allows doctors to make the diagnosis. Initially the condition can typically be corrected with glasses or soft contact lenses. As the disease progresses, special contact lenses (such as scleral contact lenses) may be required. In most people the disease stabilizes after a few years without severe vision problems. In 2016, the FDA approved corneal collagen cross-linking to halt the progression of keratoconus.
Evaluation of docetaxel pharmacokinetics in phase II and III clinical studies were with 100 mg/m2 dosages given over one-hour infusions every three weeks.Docetaxel was shown to be greater than 98% plasma protein bound independent of concentration at 37 °C and pH 7.4 Docetaxels plasma protein binding includes lipoproteins, alpha1 acid glycoprotein and albumin. Alpha1 acid glycoprotein is the most variable of these proteins inter-individually, especially in cancer patients and is therefore the main determinant of docetaxels plasma binding variability. Docetaxel interacted little with erythrocytes and was unaffected by the polysorbate 80 in its storage medium. Polysorbate 80 may be the cause of hypersensitivity reasons in taxanes as recent studies indicated.The concentration-time profile of docetaxel was consistent with a three-compartment pharmacokinetic model. An initial, relatively rapid decline, with an α half-life of mean 4.5 minutes is representative of distribution to peripheral compartments from the systemic circulation. A β half-life of mean 38.3 minutes and a relatively slow γ half-life of mean 12.2 hours represent the slow efflux of docetaxel from the peripheral compartment.Administration a 100 mg/m2 dose over a one-hour infusion gave a mean total body clearance of 21 L/h/m2 and a mean steady state volume of distribution of 73.8 L/m2 or 123 L based on the mean BSA (body surface area) of 1.68 m2. Area under the plasma concentration-time curve had a mean value of 2.8 mg.h/L. The Cmax of docetaxel was found to be 4.15 ± 1.35 mg/L.