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

Methylprednisolone
82 ± 13 a 4.9 ± 2.3 78 ± 3 6.2 ± 0.9 1.2 ± 0.2 2.3 ± 0.5 IV: 225 ± 44 ng/mL b
Metoclopramide
i LD i Fem i NS, RA, i NS, RD, RA, i NS, RD, RA, PO: 1.64 ± PO: 178 ± 44 ng/mL c
CRI, LD CRI, LD CRI, LD 0.64 c
b LD b Obes b Obes, Fem a Obes
a Fem
b Fem
a
May be decreased to 50-60% with high doses. b Mean at 1 hour following a 28-mg IV infusion
over 20 minutes given twice daily for 6 ± 4 days during the perioperative period following
kidney transplantation. c Mean data following a 24-mg oral dose given twice daily for
3 days in healthy adult male subjects.
76 ± 38 20 ± 9 40 ± 4 6.2 ± 1.3 3.4 ± 1.3 5.0 ± 1.4 A: ≤1 a A: 80 ng/mL a
i Aged, LD i RD b RD, LD i RD, a RD, LD I: 2.5 ± 0.7 a I: 18 ± 6.2 ng/mL a
LD, Aged
b Neo
b Neo
i Aged
i Aged
a
Following a single 20-mg oral dose given to healthy adults (A) or an oral (nasogastric) dose
of 0.10-0.15 mg/kg given four times daily to steady state to premature infants (I), 1-7 weeks
of age (26-36 weeks, postconceptional).
References: Kearns GL, et al. Pharmacokinetics of metoclopramide in neonates. J Clin
Pharmacol, 1998, 38:122–128. Lauritsen K, et al. Clinical pharmacokinetics of drugs used in
Metoprolol a
References: Lew KH, et al. Gender-based effects on methylprednisolone pharmacokinetics
and pharmacodynamics. Clin Pharmacol Ther, 1993, 54:402–414. Rohatagi S, et al.
Pharmacokinetics of methylprednisolone and prednisolone after single and multiple oral
administration. J Clin Pharmacol, 1997, 37:916–925. Tornatore KM, et al.
Methylprednisolone and cortisol metabolism during the early post-renal transplant period.
Clin Transplant, 1995, 9:427–432.
the treatment of gastrointestinal diseases (part I). Clin Pharmacokinet, 1990, 19:11–31.
Rotmensch HH, et al. Comparative central nervous system effects and pharmacokinetics of
neu-metoclopramide and metoclopramide in healthy volunteers. J Clin Pharmacol, 1997,
37:222–228.
38 ± 14 b 10 ± 3 b 11 ± 1 15 ± 3 b 4.2 ± 0.7 3.2 ± 0.2 b EM: ~2 c EM: 99 ± 53 ng/mL c
a LD i Preg a HTh, Preg a Fem a LD, Neo PM: ~3 c PM: 262 ± 29 ng/mL c
b Preg i Aged, Smk i Aged, HTh,
Preg, Smk
a Fem
a
Data for racemic mixture reported. Metabolism of less active R-(+)-enantiomer (CL/F =
28 mL/min/kg; V area
/F = 7.6 L/kg; t 1/2
= 2.7 hours) is slightly faster than that of more active
S-(−)-enantiomer (CL/F = 20 mL/min/kg; V area
/F = 5.5 L/kg; t 1/2
= 3 hours). b Metabolically
cleared by CYP2D6 (polymorphic). Compared to extensive metabolizers (EM), individuals
who are poor metabolizers (PM) have a lower CL/F, and a longer t 1/2
(7.6 ± 1.5 versus 2.8 ±
1.2 hours) and excrete more unchanged drug in urine (15 ± 7% versus 3.2 ± 3%) due to
reduced hepatic metabolism. c C 3 hours
following a single 100-mg oral dose in CYP2D6 EM
and PM patients with hypertension. Plasma concentrations of the more active S-enantiomer
are ~35% higher than the R-antipode in CYP2D6 EM. No stereochemical difference was
observed in PM subjects. EC 50
for decreased heart rate during peak submaximal exercise testing
was 16 ± 7 ng/mL; EC 50
for decreased systolic blood pressure during exercise testing was
25 ± 18 ng/mL.
References: Dayer P, et al. Interindividual variation of beta-adrenoceptor blocking drugs,
plasma concentration and effect: Influence of genetic status on behaviour of atenolol, bopindolol
and metoprolol. Eur J Clin Pharmacol, 1985, 28:149–153. Lennard MS, et al. Oxidation
phenotype—A major determinant of metoprolol metabolism and response. N Engl J Med,
1982, 307:1558–1560. McGourty JC, et al. Metoprolol metabolism and debrisoquine oxidation
polymorphism—Population and family studies. Br J Clin Pharmacol, 1985, 20:555–566.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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