Glucocorticoid pharmacokinetics

Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsai J-J, Frew AJ, Kay AB Glucocorticoid resistance in chronic asthma glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis 1991 144 1016-1025. 

Edsbacker S, Szefler S. Glucocorticoid pharmacokinetics principles and applications. In Schleimer RP, Busse WW, O Byme P, eds. Inhaled Glucocorticoids in Asthma Mechanisms and Clinical Actions. New York Marcel Dekker, 1997 381-445. 

Macleod, A.D., Tolentino, L., and Tozer, T.N., Glucocorticoid-dextran conjugates as potential prodrugs for colon-specific delivery steady-state pharmacokinetics in the rat, Biopharm. DrugDisp., 15 151-161 (1994). 

Pharmacokinetics Hydrocortisone and most of its congeners are readily absorbed from the Gl tract altered onsets and durations are usually achieved with injections of suspensions and esters. Hydrocortisone is metabolized by the liver, which is the rate-limiting step in its clearance. The metabolism and excretion of the synthetic glucocorticoids generally parallel hydrocortisone. Induction of hepatic enzymes will increase the metabolic clearance of hydrocortisone and the synthetic... 

Derendorf H, MoUmann H, Gruner A, Haack D, Gy-selhy G. Pharmacokinetics and pharmacodynomics of glucocorticoid suspensions after intra-articular administration. Clin Pharmacol Ther 1986 39 313-7. 

Smith MA, Davidson J, Ritchie JG, et al The corticotropin-releasing hormone test in patients with post-traumatic stress order. Biol Psychiatry 26 349-355, 1989 Smith MA, Makino S, Kvetnansky R, et al Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15 1768-1777, 1995 Smith RB, Divoll M, Gillespie WR, et al Effect of subject age and gender on the pharmacokinetics of oral triazolam and temazepam. J Chn Psychopharmacol 3 172-176, 1983... 

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). 

In patients with acute hepatitis and active hepatitis, protein binding of the glucocorticoids will be reduced and peak concentrations of administered glucocorticoids increased. Conversion of prednisone to prednisolone has been reported to be impaired in chronic active liver disease (409). However, although plasma prednisolone concentrations were more predictable after the administration of prednisolone than of prednisone to a group of healthy subjects (410), there was no difference in patients with chronic active hepatitis. There was also impaired elimination of prednisolone in these patients. In a review of the pharmacokinetics of prednisone and prednisolone it was concluded that fear of inadequate conversion of prednisone into prednisolone was not justified (411). Patients with hepatic disease suffer adrenal suppression more readily (111). 

Czock D, Keller F, Rasche FM, Haussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005 44 61-98. 

Pharmacokinetic Considerations in the Design of Pulmonary Drug Delivery Systems for Glucocorticoids... 

The pharmacokinetic/dynamic parameters involved in pulmonary dmg delivery of glucocorticoids have been reviewed. Among these, low oral bioavailability, high pulmonary deposition, pronounced clearance, and sustained pulmonary release are the most important parameters to be considered. 

M. Johnson, Pharmacodynamics and pharmacokinetics of inhaled glucocorticoids, J. Allergy Clin. Immunol. 97 169 (1996). 

G. Hochhaus, L.-S. Chen, A. Ratka, P. Druzgala, J. Howes, N. Bodor, and H. De-rendorf, Pharmacokinetic characterization and tissue distribution of the new glucocorticoid soft drug loteprednol etabonate in rats and dogs, J. Pharm. Sci. 81 1210 (1992). 

Nakajima M, Suzuki T, Sasaki T, Yokoi T, Hosoyamada A, Yamamoto T, Kuroiwa Y. Effects of chronic administration of glucocorticoid on midazolam pharmacokinetics in humans. Ther Drug Monit 1999 21(5) 507-13. 

Mechanisms of action Actions mineralocorticoid, glucocorticoid Individual adrenal steroids Pharmacokinetics Dosage schedules Choice of adrenal steroid Adverse effects of systemic pharmacotherapy Adrenal steroids and pregnancy Precautions during chronic therapy treatment of intercurrent illness Dosage and routes of administration indications for use... 

Hydrocortisone, USP, Hydrocortisone. 11/3,17.21-tri-hydraxyprcgn-4-cnc-3.2().dionc. is the primary natural glu-vocorlieoid in humans. Despite the large number of synthetic glucocorticoids, hydrocortisone, its esters, and its salts rc-in.tin a mainstay of modem adrenocortical steroid therapy iind Ihe standard for comparison of all other glucocorticoids and mineraliKorticoids (sec Table 2.3-8). It is used for all the indications mentioned above. Its esters and. salts illustrate Ihe principles of chemical modification to modify pharmacokinetic use shown in Figure 2.3-6. The commercially available salts and esters (sec Fig. 23-30) include... 

Z. X. Xu, Y. N. Sun, D. C. DuBois, R. R. Ahnon, and W. J. Jusko, Third-generation model for corticosteroid pharmacodynamics roles of glucocorticoid receptor mRNA and tyrosine aminotransferase mRNA in rat liver. I Pharmacokinet Biopharm 23(2) 163-181 (1995). 

The pharmacokinetics of the glucocorticoids varies with the agent given and the route of administration. In general, most steroids... 

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