Hydrocortisone Prednisolone

Methylation of hydrocortisone/prednisolone ia positions C-4, C-7, C-12, and C-21 failed to give useful products. Methylation at C-16, ia contrast, led to 16a- and 16P-methyl-9a- uoroprednisolones which were exceptionally useful. Both series were prepared usiag 3a-acetoxy-5a-pregn-16-ene-ll,20-dione derived from desoxychoHc acid (80). A much shorter route was subsequentiy developed from... 

A third advancement in microbial biotechnology of steroid production was the abiUty to introduce a 16a-hydroxyl group microbiologicaHy (163). Modifications of the liP-hydroxylation, 16a-hydroxylation 1,2-dehydrogenation microbial processes are used for the synthesis of hydrocortisone, prednisolone, triamcinolone, and other steroid pharmaceuticals. A few microbial transformations that have been used to manufacture steroids are Hsted in Table 1 (164). 

Benzoic acids substituted with a basic side chain also are also of interest as pro-moieties whose physicochemical properties and rates of enzymatic hydrolysis can readily be modulated. A number of drugs have been converted to prodrugs with this type of pro-moiety, e.g., hydrocortisone, prednisolone, acyclovir, chloramphenicol, and paracetamol [148] [149], These prodrugs appear well suited as parenteral formulations, being water-soluble, stable in slightly acidic solution, and readily hydrolyzed enzymatically. As examples, we consider here the hydrolysis in human plasma of a number of (aminomethyl)ben-zoates of metronidazole (8.109-8.115, Sect. 8.5.5.1, Table 8.9) [138], These prodrugs are very rapidly activated, which may be beneficial for parenteral administration. However, this type of pro-moiety may be cleaved too rapidly after oral administration to be of interest for poorly absorbed drugs. 

Corticosteroids - prednisone, hydrocortisone, prednisolone also nonsteroidal anti- inflammatory drugs, aspirin... 

Cortisone and hydrocortisone (cortisol) are enzymatically interconvertible, and so one finds metabolites from both. Glucocorticoids having a ketone group at Cn (e.g., cortisone, prednisone, and meprednisone) must be reduced in the liver to their corresponding 11 J-hydroxyl analogs (hydrocortisone, prednisolone, and meprednisolone) in order to be pharmacologically active. 

The present type of thermosensitive gel has been applied in the immobilization of Arthrobacter simplex cells, and the bioconversion of a steroid (hydrocortisone -> prednisolone by 3-ketosteroid-A1-dehydrogenase in A. simplex) was examined using the thermal cycling method [65]. In this case, the thermal cycling was... 

Tixocortol pivalate is a marker for glucocorticoid contact allergy, as a positive patch test suggests established contact allergy to hydrocortisone, prednisolone, and their derivatives (95). A literature search via Medline from 1966 to May 2000 revealed only one patient hypersensitive to tixocortol pivalate and budesonide in a pilot study in 34 patients (10 with asthma, 13 with rhinitis, 11 with both) (96). From case reports, the prevalence of glucocorticoid-induced contact allergy has been estimated at 2.9-5%. 

Steroids (hydrocortisone, prednisolone, betamethasone, adrenosterone, fluocortolone,...)... 

Triamcinolone, hydrocortisone, prednisolone, cortisone, methylprednisolone, betamethasone, dexamethasone, adrenosterone, fluocortolone, triamcinolone acetonide Hypersil Cl8, 3 pm Acetonitrile-5 mM ammonium acetate, gradient from 17 83 to 38 62 420 mm x 50 pm i.d. 300 mm packed length... 

Hydrocortisone, prednisolone, hydrocortisone-21 -acetate, testosterone Poly(AMPS-co-IPAAm) hydrogel 100 mM Tris-150 mM boric acid, pH 8.1 650 mm x 75 pm i.d. 500 mm packed length... 

Hydrocortisone, prednisolone, betamethasone, betamethasone dipropionate, clobetasol butyrate, fluticasone propionate, clobetasone butyrate, betamethasone-17-valerate Hypersil Cl8, 3 pm Acetonitrile-2 mM phosphate, pH 7.8 (80 20) 270 mm x 50 pm i.d. 200 mm packed length... 

Dexamethasone, hydrocortisone, prednisolone acetate, cortisone acetate Hypersil C8, 3 pm... 

Prednisolone is extensively bound to plasma proteins, although less so than hydrocortisone. Prednisolone is a corticosteroid with mainly glucocorticoid activity in fact, 5 mg prednisolone is equivalent in anti-inflammatory activity to ca. 

Hydrocortisone, prednisolone, betamethasone, betamethasone dipropionate, clobetasol butyrate, fluticasone propionate, clobetase butyrate, betamethasone-17-valerate... 

CORTICOSTEROIDS PROTEASE INHIBITORS-RITONAVIR t plasma levels of betamethasone, dexamethasone, hydrocortisone, prednisolone and both inhaled and intranasal budesonide and fluticasone with ritonavir (with or without lopinavir) Inhibition of CYP3A4-mediated metabolism Monitor closely for signs of corticosteroid toxicity and immunosupression, and i dose as necessaiy. Consider using inhaled bedometasone... 

Intra-articular injection of corticosteroid (triamcinolone, hydrocortisone, prednisolone or dex-amethasone) is very effective when one joint is more affected than others. Benefit from one injection may last many weeks. Aseptic precautions must be extreme, for any introduced infection may spread dramatically. Too frequent resort to corticosteroid injection may actually promote joint damage by removing the protective limitation conferred by pain such injections in a single joint would not normally exceed three per year. Other aspects of the treatment of inflammatory arthritis are important but are outside the scope of this book. 

The therapeutic effectiveness of topically applied corticosteroids is attributed primarily to their antiinflammatory activity. The relative efficacy of topical corticosteroids appears to be in the following order hydrocortisone, prednisolone, betamethasone < hydrocortisone valerate or butyrate, betamethasone valerate, triamcinolone acetonide, flucinolone acetonide < betamethasone dipropionate, fluocino-nide. In addition to the nature of the corticosteroid, its solubility, and, to a lesser extent, the concentration used, clinical efficacy is influenced by the formulation of the preparation. Glucocorticoids appear to have greater efficacy when formulated in ointment bases than in cream or lotion vehicles. This could be attributed to the occlusive effect provided by ointments. The application of an occlusive dressing further enhances penetration and persistence of the steroid (reservoir effect) in the stratum corneum. " ... 

Local injection can be effective, e.g. into the affected region in tendinitis, or sometimes intrathecally. Systemic administration is normally reserved for short-term use or emergencies, such as anaphylactic shock. Examples of this type include betamethasone, clobetasol, cortisone, hydrocortisone, prednisolone and triamcinolone. 

Simultaneous metabolites, cortisone, hydrocortisone, prednisolone, prednisone... 

Simultaneous betamethasone, cortisone, dexamethasone, hydrocortisone, prednisolone Interfering prednisone... 

Extracted hydrocortisone, prednisolone Simultaneous hydrocortisone, prednisolone... 

---