Dose‐dependent prednisolone kinetics

Abstract

Although prednisone and prednisolone have been in use for a number of years for a wide variety of conditions, there have been few kinetic studies over the wide clinical dosage range. 5 • 9, 10, 12, 13, 15 It has been documented same subject are reproducible. 14 The conclusions from two recent studies lo , 12 in a small number of subjects given 5 to 50 mg of prednisolone or prednisone have shown that there are dose-dependent changes in the kinetics of prednisolone in man with a prolongation of half-life (t1/2)/0, 12 an increase in volume of distribution (V d)10 and plasma clearance 10,12 with increasing dose. In addition, it was noted by Meikle and TylerB that the 24-hr doseresponse to 70 mg prednisone deviated significantly from dose-response curves at lower dosages.that there is considerable interindividual variation in pharmacokinetic measurements at any single dose,4, 15 although separate studies on the Prednisone has very little intrinsic glucocorticoid activity I and has to be converted to pred-0009-9236/79/050571+08$00.80/0

Biowaiver Monographs for Immediate Release Solid OralDosage Forms: Prednisolone

“…The systemic availability is almost complete and reported to range from 75% to 98%, [11], [14], [30][31][32][33][34][35][36][37][38][39] with a concentration-time profile that is very similar to that when prednisone is taken orally. [40], [41] Maximum serum concentrations occur within 1-2 h after administration of a single dose.…”

“…[40], [41] Maximum serum concentrations occur within 1-2 h after administration of a single dose. [10], [11], [14], [31], [32], [35], [42][43][44] Food intake prolongs the time to peak concentration, but does not affect the extent of absorption. [45][46][47] No indication of existence of an absorption window was found in the literature.…”

“…[31], [44], [49] With increasing dose, the volume of distribution of prednisolone increases, due to a shift in a larger fraction of the body burden from the plasma compartment to other body tissues or to sites of greater metabolic activity. [44] The concentration-dependent binding of prednisolone to the plasma proteins (i.e., transcortin and albumin) results in the dose-dependent nonlinear pharmacokinetics observed for prednisolone.…”

“…[44], [58] The nonlinear interconversion varies with time and dose. [11], [31], [44], [49], [59][60][61][62] The serum half-life of prednisolone is known to be 2-4 h, [10], [11], [32], [33], [39], [44], [46] and may be influenced by time of day, age, gender, physical exercise, pregnancy, drugs, and several diseases. [14] Prednisolone is cleared from the body primarily by hepatic metabolism by hydroxylation and reduction forming metabolites which conjugate with glucuronic acid and sulfate.…”

“…Approximately 2%-5% is excreted in the urine as prednisone. [44] The clearance of prednisolone is dose-dependent, [31][32][33], [44], [59], [60,64] due to the concentration-dependent protein binding, that is, at high doses the increased free fraction of prednisolone is reflected in a greater plasma clearance and apparent volume of distribution. The total body clearance of prednisolone has been reported to be 111 mL/min/1.73 m2 for a 5 mg dose and 194 mL/min/1.73 m2 for a 40 mg dose of prednisolone.…”