Prednisolone half-life

Nine patients with rheumatoid arthritis taking prednisolone 8 to 15 mg daily had strong evidenee of elinieal deterioration (worsening joint tenderness, pain, morning stiffness, fall in grip strength) when they took pheno-barbital for 2 weeks (plasma levels 0 to 86.2 micromol/L). The prednisolone half-life fell by 25%. ... 

Pfiarmacokinetics Well absorbed from the GI tract. Protein binding 70%-90%. Widely distributed. Metabolized in the liver and converted to prednisolone. Primarily excreted in urine. Not removed by hemodialysis. Half-life 3.4-3.8 hr. 

Significant differences in the pharmacokinetics of prednisolone amongst menopausal women have been described (SEDA-21, 419 412). The postmenopausal women had reduced unbound clearance (30%), reduced total clearance, and an increased half-life. Similar results are seen in the postmenopausal women who took estrogen or estrogen-progestogen therapy. 

Peak plasma concentrations of prednisolone are reached 1-2 h after oral dosing, and the plasma half-life is 2-4 h. 

Methylprednisolone may be slightly less likely than prednisolone to cause sodium and water retention. It is fairly rapidly distributed following oral administration, with a plasma half-life of 3.5 h or more. The tissue half-life is reported to range from 18 to 36 h. 

Factors contributing to the reduced propensity of some steroids to raise lOP could include their intraocular bioavailability, considerably shorter pharmacokinetic half-life, and greater susceptibility to metabolism as compared with dexamethasone and prednisolone. In addition to the individual steroid s effect on lOP, concentration, frequency, and length of administration may play a role in lOP elevation. 

Prednisone is converted to active prednisolone in the body and has multiple effects on the immune system. Prednisone is very well absorbed from the gastrointestinal (GI) tract and has a long biologic half-life, so it can be dosed once daily. 

Synthetic glucocorticoids The mechanism of action of these agents is identical to that of cortisol. A large number are available for use prednisone and its active metabolite, prednisolone, dexamethasone, and triamcinolone are representative. Their properties (when compared to cortisol) include longer half-life and duration of action, reduced salt-retaining effect, and better penetration of lipid barriers for topical activity (Table 39-1). 

Prednisolone sodium phosphate is the water-soluble sodium salt of the 21-phosphate ester, with a half-life of less than 5 minutes because of rapid hydrolysis by phosphatases (44,46). Peak plasma levels for prednisolone are attained in approximately 10 minutes following its administration by injection (usual dose of 20 mg IV or IM). Topically, one or two drops of a 0.5% solution may be used four to six times daily for its anti-inflammatory action in the eye. 

The plasma half-life of prednisolone following the oral administration of prednisone to normal subjects ranges form 2.5 to 3.5 h (126, 130, 131). Similar half-life values for prednisolone were observed after oral prednisolone is administered (126, 132, 133, 134). Nugent et al (135) found after an intravenous dose of 1 mg/kg body weight of prednisolone (sodium succinate salt) an average half-life of 3.5 h. After an intravenous dose of 0.3 mg/kg prednisolone as phosphate the mean plasma... 

The plasma clearance, half-life and volume of distribution of prednisolone is reported to be independent in the range of the doses 10, 20 and 30 mg prednisolone adminstered orally (139). Pickup et al (140) studied pharmacokinetics of prednisolone at different levels in ten subjects, four normal subjects and six patients with osteoarthritis after intravenous administration of prednisolone. Average prednisolone half-lives were found to be between 2.6 to 3.8 h, mean volume distribution between 0.22 to 0.64 1/kg, and plasma clearance between 1.02 to 2.0 ml/min/kg following the tracer 0.15 mg/kg and 0.3 mg/kg doses. This data showed sginificant increases in volume of distribution and plasma clearance of prednisolone with inceasing dose. An increase in half-life was also observed. Pickup et al. (140) thus postulate that the observed dose-dependent kinetics is primarily due to the non-linearity in... 

In another study the area under the plasma concentration-time curve for prednisolone for the 20 mg dose was 77.89 % of that calculated for the 10 mg dose. This change in area represented an increase in prednisolone clearance from 1,7 ml/min kg to 2.2 ml/min kg when the dose was increased (141). Rose et al. (142) found dose-dependent pharmacokinetics of prednisolone where the plasma half-life increased from 3 to 5 h as the oral dose of prednisone was increased from 5 to 50 mg. Tanner et al (143) reported the pharmacokinetics of prednisolone at different dose levels in 43 subjects. Each subject received only a single dose, 5 - 200 mg of oral prednisolone. Kinetic parameters of oral prednisolone are presented in table 5 and fig. 13 illustrates concentration-time profile of prednisolone. The mean half-life of prednisolone remained fairly constant between 3.4 to 3.8 h. Bioavailability of prednisolone was 98.5 i 4 %. Furthermore as the prednisolone dose increased, the area under the curve increased but not proportionally to the dose, such that a fivefold increase in dose from 20 to 100 mg resulted in only a two-to threefold increase in area under the curve. 

It appears that prednisolone may exhibit dose-dependent pharmacokinetics, so that with increasing dose values volume of distribution, plasma clearance and half-life may increase. It is believed to be related to changes in the plasma protein binding of prednisolone. Prednisolone appears to bind to plasma proteins in a non linear manner over the range of doses used (131). 

Figure 3.10 Semilogarithmic plot of plasma concentration (Cp) versus time following administration of the drug prednisolone by intravenous bolus injection. Such a plot permits the determination of the elimination half life (ti/2) and the elimination rate constant (k). (Cp)o, initial plasma concentration.

Eight patients with heart transplants taking ciclosporin 8 mg/kg daily, prednisolone and azathioprine for at least one month, were given roxithromycin 150 mg twice daily for 11 days. A 37.5% rise in plasma ciclosporin levels occurred at the time the roxithromycin was given, and a 60% rise occurred 4 hours later. Ciclosporin levels fell again when the roxithromycin was stopped. A small (10%) increase in serum creatinine levels occurred. There was no evidence of a deterioration in renal function. The half-life of roxithromycin was found in one study to be doubled, from 17 to 34.4 hours, in patients with kidney transplants who were taking ciclosporin. ... 

A study in 8 patients receiving long-term treatment with carbamazepine found that the elimination half-life of prednisolone was about 45 minutes shorter, and the clearanee was 42% higher, than in 9 healthy subjects not taking carbamazepine. ... 

ALA-synthetase has one of the shortest half-lives yet reported for any mammalian liver enzyme, even the inducible ones. In contrast, the half-lives of two other mitochondrial enzymes, alanine and ornithine-amino transferases, inducible by the corticosteroid prednisolone acetate in a concentration of 0.5 mg/rat/day was 17 to 24 hours [75]. The short half-life of ALA-synthetase apparently depends on other cell constituents. When mitochondria from induced guinea pigs were isolated, the activity of their ALA-synthetase was maintained constant over a period of at least 5 hours [35] this activity may have finally not been limited by the stability of the enzyme itself but by the succinyl-CoA-synthesizing mechanism of the mitochondria. These facts suggest that there may be an active process of ALA-synthetase destruction which occurs in the cells but not necessarily in the isolated mitochondria, and which is not affected by the inducing chemicals such as DDC or AIA. 

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