DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
Table AII–1
Pharmacokinetic Data (Continued)
BIOAVAILABILITY URINARY BOUND IN CLEARANCE VOL. DIST. HALF-LIFE PEAK TIME PEAK
(ORAL) (%) EXCRETION (%) PLASMA (%) (mL/min/kg) (L/kg) (hours) (hours) CONCENTRATION
Prednisolone
82 ± 13 26 ± 9 a 90-95 1.0 ± 0.16 c 0.42 ± 0.11 e 2.2 ± 0.5 1.5 ± 0.5 f 458 ± 150 ng/mL f
(<200 ng/mL) b
i Hep, Cush, a Aged, HTh ~70 i Hep, Cush, i Hep, Cush, i Hep, Cush,
RD, Crohn, (>1 μg/mL) Smk, CRI, Smk, RD, Smk, RD,
Celiac, b Alb, NS, NS, d CRI, NS d CRI, NS d
Smk, Aged Aged, HTh, HTh d b HTh, d
b HTh LD b Aged, d LD d Aged, Obes d b HTh d
i Hep
a Aged d
a
Prednisolone and prednisone are interconvertible; an additional 3 ± 2% is excreted as prednisone.
b Extent of binding to plasma proteins is dependent on concentration over range
encountered. c Total CL increases as protein binding is saturated. CL of unbound drug
increases slightly but significantly with increasing dose. d Changes are for unbound drug.
e
V increases with dose due to saturable protein binding. f Following a 30-mg oral dose given
twice daily for 3 days to healthy adult male subjects. The ratio of prednisolone/prednisone is
Prednisone
dose dependent and can vary from 3-26 over a prednisolone concentration range of 50-800
ng/mL.
References: Frey BM, et al. Clinical pharmacokinetics of prednisone and prednisolone. Clin
Pharmacokinet, 1990, 19:126–146. Rohatagi S, et al. Pharmacokinetics of methylprednisolone
and prednisolone after single and multiple oral administration. J Clin Pharmacol,
1997, 37:916–925.
80 ± 11 a 3 ± 2 b 75 ± 2 c 3.6 ± 0.8 d 0.97 ± 0.11 d 3.6 ± 0.4 d P: 2.1-3.1 e P: 62-81 ng/mL e
i Hep, Cush, i HTh i Hep i Hep i Smk, Hep PL: 1.2-2.6 e PL: 198-239 ng/mL e
RD, Crohn,
Celiac, Smk,
Aged
a
Measured relative to equivalent IV dose of prednisolone (PL). b An additional 15 ± 5%
excreted as PL. c In contrast to PL, there is no dependence on concentration. d Kinetic values
for prednisone (P) often are reported in terms of values for PL, its active metabolite. However,
the values cited here pertain to P. e Range of mean data for P and PL following a single 10-mg
oral dose given as different proprietary formulations to healthy adults.
References: Gustavson LE, et al. The macromolecular binding of prednisone in plasma of
healthy volunteers including pregnant women and oral contraceptive users. J Pharmacokinet
Biopharm, 1985, 13:561–569. Pickup ME. Clinical pharmacokinetics of prednisone and prednisolone.
Clin Pharmacokinet, 1979, 4:111–128. Sullivan TJ, et al. Comparative bioavailability:
Eight commercial prednisone tablets. J Pharmacokinet Biopharm, 1976, 4:157–172.