Studies with oral and intravenous dosing of radiolabeled ciclesonide have shown an incomplete extent of oral absorption (%). The oral bioavailability of both ciclesonide and the active metabolite is negligible (<% for ciclesonide, <1% for the metabolite). Based on a γ-scintigraphy experiment, lung deposition in healthy subjects is 52%. In line with this figure, the systemic bioavailability for the active metabolite is >50% by using the ciclesonide metered dose inhaler. As the oral bioavailability for the active metabolite is <1%, the swallowed portion of the inhaled ciclesonide does not contribute to systemic absorption.
Progesterone is produced from cholesterol with pregnenolone as a metabolic intermediate . In the first step in the steroidogenic pathway , cholesterol is converted into pregnenolone, which serves as the precursor to the progestogens progesterone and 17α-hydroxyprogesterone. These progestogens, along with another steroid, 17α-hydroxypregnenolone , are the precursors of all other endogenous steroids, including the androgens, estrogens, glucocorticoids, mineralocorticoids, and neurosteroids. Thus, many tissues producing steroids, including the adrenal glands , testes , and ovaries , produce progestogens.
Stikkelbroeck et al. (2001) investigated the prevalence of testicular tumors in 17 adolescent and adult male patients with CAH aged 16 to 40 years. In 16 of 17 patients, one or more testicular tumors ranging in maximal length from to cm were found on ultrasonography. In 6 patients, the testicular tumors were palpable. Undertreatment, defined as the presence of a salivary androstenedione level above the upper reference morning level, was found in 5 of 17 patients at the time of investigation. The other 12 patients were treated adequately or even overtreated at the time of investigation. Nevertheless, 11 of these 12 patients showed testicular tumors on ultrasonography. Tumor size was significantly larger in patients who were heterozygous or homozygous for deletion or conversion of the CYP21 gene than in patients who did not have this genotype. Impairment of Leydig cell function as manifested by decreased plasma levels of testosterone was found in 6 of 17 patients. Semen analysis in 11 patients revealed azoospermia in 3 patients and poor semen quality in 4 patients. The authors concluded that, when carefully sought for, testicular adrenal rest tumors are frequently present in adolescent and adult males with CAH and are often accompanied by impaired spermatogenesis and Leydig cell failure.