6«-Methyl prednisolone

Like in Chapt. 7, we begin the discussion with acetates, since acetic acid is the simplest nontoxic acyl group, formic acid being less innocuous. An informative study was carried out to compare the kinetics of hydrolysis of two types of corticosteroid esters, namely methyl steroid-21-oates (which are active per se) and acetyl steroid-21-ols (which are prodrugs), as exemplified by methyl prednisolonate (8.69) and prednisolone-21-acetate (8.70), respectively [89]. In the presence of rat liver microsomes, the rate of hydrolytic inactivation of methyl steroid-21-oates was much slower than the rate of hydrolytic activation of acetyl steroid-21-ols. Thus, while the Km values were ca. 0.1 -0.3 mM for all substrates, the acetic acid ester prodrugs and the methyl ester drugs had Vmax values of ca. 20 and 0.15 nmol min-1 mg-1, respectively. It can be postulated that the observed rates of hydrolysis were determined by the acyl moiety, in other words by the liberation of the carboxylic acid from the acyl-enzyme intermediate (see Chapt. 3). 

One interesting feature of stability is that a product may have two shelf lives, one for the manufactured material and another for the reconstituted or opened pack. Methyl prednisolone sodium succinate lyophihsed injection, for example, is stable for up to 3 years in the dry state but the reconstituted injection must be used within 12 h. 

The mineralocorticosteroid activity of methyl-prednisolone is even less than that of prednisone/ prednisolone. It has a comparable duration of action. It is less suitable for substitution therapy in patients with adrenal hypofunctional states. Methyl-prednisolone sodium succinate is formulated for parental administration while methylprednisolone acetate is used for intra-articularly or peri-articularly injections. It can also be administered IM and then has prolonged systemic effects, lasting 1 weeks as the acetate is absorbed slowly from the site of injection. Oral absorption is rapid with peak effects within 1-2 hours. The duration of action is then about 1.5 days. 

Another review of nine trials including a total of 344 adult patients concludes that no differences can be identified among the different doses of corticosteroids in acute asthma requiring hospital admission. Low dose corticosteroids 80 mg/day of methyl-prednisolone or <400 mg/day of hydrocortisone) appear to be adequate in the initial management of these adult patients. Higher doses do not appear to offer a therapeutic advantage. 

System (2) has been employed for the determination of cortisol and cortisone in urine [150]. Urine containing 6a-methyl prednisolone as an internal standard was applied to a Sep-Pak Cig cartridge, eluted with aqueous 90% acetonitrile, and the eluent analyzed by HPLC. The analytical column (25 cm x 4.6 mm) is packed with Altex Ultrasphere C s bonded silica (5 pm), and requires the use of a (5 cm x 5 mm) Hypercil ODS (5 pm) pre-column. The mobile phase used gradient elution with less than 100% acetonitrile, and detection is by UV absorbance at 260 nm. 

Methyl Prednisolone Aceponate Cream For atopic dermatitis... 

In an early study Turpeinen and Stenman [99] published a negative-ion MRM ES-MS/MS method for urinary cortisol. The internal standard used was 6a-methyl-prednisolone and manual extraction was employed. Both steroids eluted within 6 min from the microbore column, but the total run and equilibration time was not reported. The transitions monitored were m/z 361—>331 for cortisol and m/z 373—> 343 for internal standard. The sample size was 1 ml. 

Methyl prednisolone Muromonab-CD3 Mycophenolate Mofetil Prednisone Tacrolimus Basiliximab Daclizumab Sirolimus... 

Serious cardiac dysrhythmias and sudden death have been reported with pulsed methylprednisolone. Oral methyl-prednisolone has been implicated in a case of sinus bradycardia (31). 

Perforation of the sigmoid colon occurred in a 61-year-old Caucasian man with colonic diverticular disease and rheumatoid arthritis treated with pulses of methyl-prednisolone 1 g (153). 

In a review of renal transplantation during 1974—94,166 patients were classified into those with osteonecrosis of the femoral head (22 patients) and those without (47 patients) (SEDA-21, 417 226). The total dose of methyl-prednisolone was higher in those with osteonecrosis. All... 

Significant differences in the pharmacokinetics of methyl-prednisolone have been described in black and white renal transplant patients. Black patients had a slower clearance rate and a lower apparent volume of distribution. They had higher cortisol concentrations throughout the day, with higher nadir concentrations. Some of them had glucocorticoid-associated diabetes, and no white patients did. Further studies are needed to define the differences between the races (SEDA-20, 377 404). 

Of 31 patients who received 1 ml (40 mg) of methyl-prednisolone epidurally at the end of microdiscectomy, three developed epidural abscesses (459). These results were compared with a historical series of 400 patients not taking glucocorticoids, who had no deep infection. Although the data were limited, epidural glucocorticoids after discectomy should not be recommended. 

Saisu T, Sakamoto K, Yamada K, Kashiwabara H, Yokoyama T, Iida S, Harada Y, Ikenoue S, Sakamoto M, Moriya H. High incidence of osteonecrosis of femoral head in patients receiving more than 2 g of intravenous methyl-prednisolone after renal transplantation Transplant Proc 1996 28(3) 1559-60. 

Moreno-Ancillo A, Martin-Munoz F, Martin-Barroso JA, Diaz-Pena JM, Ojeda JA. Anaphylaxis to 6-alpha-methyl-prednisolone in an eight-year-old child. J Allergy Clin Immunol 1996 97(5) 1169-71. 

Clear D. Anaphylactoid reaction to methyl prednisolone developing after starting treatment with interferon beta-lb. J Neurol Neurosurg Psychiatry 1999 66(5) 690. 

Anderson, B. D., R. A. Conradi, and K. Johnson. 1983.ilBnce of premicellar and micellar association on the reactivity of methyl prednisolone 21-hemiesters in aqueous solutifRharm. Sci72 448-454. 

There is no cure for SLE. Guillermo el al. (G16) found only 10 randomized controlled trials during the past 5 years, 5 for lupus nephritis and 5 for all SLE patients. Compared to conventional therapies for lupus nephritis, a monthly bolus with intravenous cyclophosphamide is more effective than a monthly bolus with methyl prednisolone, but has significant side effects (including amenorrhea, cervical dysplasia, avascular necrosis, and herpes zoster) in both groups (G14). In order to avoid these side effects, more recent therapies have been developed. However, neither plasmapheresis (Wl), intravenous immunoglobulin (B21), recombinant human DNase (rhDNase) (D3), nor mycophenolate mofetil (C14) was shown to be more effective than conventional therapy. However, some of these... 

Three other randomized, placebo-controlled studies (14-16) investigated the influence of intravenous methyl prednisolone before angioplasty with negative results. In these studies, l,0g methyl prednisolone was infused intravenously... 

The most commonly described USP procedure for quantification is the scrap and elution approach. Low analyte recoveries can occur but can be minimized by using polar organic solvents such as methanol, ethanol, or acetone. Generally, analytes with high-Rf values can be desorbed with high recoveries by using the mobile phase. One example of this procedure is the USP assay procedure of the steroid methyl prednisolone acetate in cream formulation. This steroid is separated from its excipients by TLC, extracted from the sorbent, derivatized, and measured spectrophotometrically. 

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