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

Cyclosporine
SI: 28 ± 18 a,b <1 93 ± 2 5.7 (0.6-24) b,c 4.5 (0.12-15.5) b 10.7 (4.3-53) b NL: 1.5-2.0 d NL: 1333 ±
469 ng/mL d
b Hep, LD, b Aged i Aged b Child
Aged
i RD a Child b Child SI: 1101 ±
a Child
570 ng/mL d
a NEORAL (NL) exhibits a more uniform and slightly greater (125-150%) relative oral bioavailability
than the SANDIMMUNE (SI) formulation. b Pharmacokinetic parameters based on measurements
in blood with a specific assay. Data from renal transplant patients shown.
c
Metabolized by CYP3A to three major metabolites, which are subsequently biotransformed
to numerous secondary and tertiary metabolites. d Steady-state C max
following a 344 ±
122-mg/day oral dose (divided into two doses) of cyclosporine (NL, soft gelatin capsule) or a
14-mg/kg/day (range 6-22 mg/kg/day) oral dose of cyclosporine (SI) given to adult renal
Cytarabine a
<20 b 11 ± 8 13 13 ± 4 2.4-2.7 c 2.6 ± 0.6 — IV, B: ~5 μg/mL d
a
Cytarabine is rapidly metabolized by deamination to non-toxic uridine arabinoside.
b
Liposome formulation of cytarabine given intrathecally. Cerebrospinal fluid t 1/2
= 100-263
hours for liposome formulation (compared to 3.4 hours for intrathecal dose of free drug).
c
V area
reported. d C max
following a single 200-mg/m 2 IV bolus (IV, B) dose or steady-state
plasma concentration following a 112-mg/m 2 /day constant-rate IV infusion (IV, I) given to
patients with leukemia, malignant melanoma, or solid tumors.
Dapsone
transplant patients in stable condition. Mean trough concentration after NL was 251 ± 116 ng/mL;
therapeutic range (trough) is 150-400 ng/mL.
References: Fahr A. Cyclosporin clinical pharmacokinetics. Clin Pharmacokinet, 1993, 24:472–495.
PDR54, 2000, pp. 2034–2035. Pollak R, et al. Cyclosporine bioavailability of Neoral and
Sandimmune in white and black de novo renal transplant recipients. Neoral Study Group.
Ther Drug Monit, 1999, 27:661–663. Ptachcinski RJ, et al. Cyclosporine kinetics in renal
transplantation. Clin Pharmacol Ther, 1985, 38:296–300.
IV, I: 0.05-0.1 μg/mL d
References: Ho DH, et al. Clinical pharmacology of l-β-D-arabinofuranosyl cytosine. Clin
Pharmacol Ther, 1971, 72:944–954. Wan SH, et al. Pharmacokinetics of l-β-D-arabinofuranosylcytosine
in humans. Cancer Res, 1974, 34:392–397.
93 ± 8 a 5-15 b 73 ± 1 0.60 ± 0.17 c 1.0 ± 0.1 22.4 ± 5.6 SD: 2.1 ± 0.8 d SD: 1.6 ± 0.4 μg/mL d
i RD, LD i LD, Child i LD i LD, Child MD: 3.3 μg/mL d
a Neo
a
Decreased in severe leprosy by (70-80%) estimates based on urinary recovery of radioactive
dose. b Urine pH = 6-7. c Undergoes reversible metabolism to a monoacetyl metabolite; the
reaction is catalyzed by NAT2 (polymorphic); also undergoes N-hydroxylation (CYP3A,
CYP2C9). d Following a single 100-mg oral dose (SD) or a 100-mg oral dose given once daily
to steady state (MD) in healthy adults.
References: Mirochnick M, et al. Pharmacokinetics of dapsone administered daily and weekly
in human immunodeficiency virus-infected children. Antimicrob Agents Chemother, 1999,
43:2586–2591.
Pieters FA, et al. The pharmacokinetics of dapsone after oral administration to healthy
volunteers. Br J Clin Pharmacol, 1986, 22:491–494.
Venkatesan K. Clinical pharmacokinetic considerations in the treatment of patients with
leprosy. Clin Pharmacokinet, 1989, 16:365–386.
Zuidema J, et al. Clinical pharmacokinetics of dapsone. Clin Pharmacokinet, 1986,
11:299–315.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
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