The β-Ο-linked glycosides (sennosides) are neither absorbed in the upper gut nor split by human digestive enzymes. They are converted by bacteria of the large intestine into the active metabolite (rhein anthrone). Aglyca are absorbed in the upper gut. Animal experiments with radio-labelled rhein anthrone administered directly into the caecum demonstrated absorption < 10%. In contact with oxygen, rhein anthrone is oxidised into the rhein and sennidins, which can be found in the blood, mainly in the form of glucuronides and suphates. After oral administration of sennosides, 3-6% of the metabolites are excreted in urine; some are excreted in bile. Most of the sennosdies (ca. 90%) are excreted in faeces as polymers (polyquinones) together with 2 – 6% of unchanged sennosides, sennidins, rhein anthrone and rhein. In human pharmacokinetic studies with senna pods powder (20 mg sennosides), administered orally for 7 days, a maximum concentration of 100ng rhein/ml was found in the blood. An accumulation of rhein was not observed. Active metabolites, . rhein, pass in small amounts into breast milk. Animal experiments demonstrated that placental passage of rhein is low.
In patients with severely impaired renal function or decreased urate clearance, the half-life of oxypurinol in the plasma is greatly prolonged. Patients should be treated with the lowest effective dose, in order to minimize possible side effects. The appropriate dose of allopurinol sodium for injection for patients with a creatinine clearance ≤10 mL/min is 100 mg per day. For patients with a creatinine clearance between 10 and 20 mL/min, a dose of 200 mg per day is recommended. With extreme renal impairment (creatinine clearance less than 3 mL/min), the interval between doses may also need to be extended.
The biosynthesis of adrenocortical steroids is now a reasonably well understood process, which proceeds by discrete, enzyme directed steps from cholesterol to the various hormonal steroids. However, much of our knowledge derives from studies of animal tissues and there is a need for further studies of human glands. In particular, the details of individual enzyme systems, and the extent and significance of compartmentalization of steroid intermediates requires further exploration. The adrenal metabolic errors also merit further study, to clarify some aspects of congenital adrenal hyperplasia and to explain the relationship between biochemical and clinical observations. The advent of immunoassay methods for the measurement of steroid hormone levels in plasma has changed the approach to diagnostic steroid endocrinology, with less emphasis now on the measurement of urinary steroid metabolites, particularly in regard to androgens. The newer and sensitive methods available also allow the assay of steroid hormones in saliva, and the ready availability of this fluid, and the fact that sampling is a non-invasive technique makes salivary steroid assay an attractive alternative to other, traditional methods of investigation requiring blood or urine collection. Inhibitors of steroid biosynthesis and of steroid action have been used with considerable success in diagnostic techniques and to a limited extent in the treatment of steroid disorders. As our understanding of the details of steroid biosynthesis, mechanism of steroid action, and control of steroid secretion improve, further progress in designing clinically useful inhibitors should be possible.