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
Buspirone a
3.9 ± 4.3 <0.1 >95 28.3 ± 10.3 5.3 ± 2.6 2.4 ± 1.1 0.71 ± 0.06 e 1.66 ± 0.21 ng/mL e
a Food b b LD, c RD d a LD, RD
a
Data from healthy adult male subjects. No significant gender differences. Undergoes extensive
CYP3A-dependent first-pass metabolism. The major metabolite (l-pyrimidinyl piperazine)
is active in some behavioral tests in animals (one-fifth potency) and accumulates in
blood to levels severalfold higher than buspirone. b Bioavailability increased ~84%; appears to
be secondary to reduced first-pass metabolism. c CL/F reduced, hepatic cirrhosis. d CL/F
reduced, mild renal impairment; unrelated to CL cr
. e Following a single 20-mg oral dose.
Busulfan
70 (44-94) 1 2.7-14 4.5 ± 0.9 a 0.99 ± 0.23 a 2.6 ± 0.5 2.6 ± 1.5 Low: 65 ± 27 ng/mL b
a
CL/F and V area
/F reported. b Following a single 4-mg oral dose (low) given to patients with
chronic myelocytic leukemia or a single 1-mg/kg oral dose (high) given as ablative therapy to
patients undergoing bone marrow transplantation.
Calcitriol a
References: Barbhaiya RH, et al. Disposition kinetics of buspirone in patients with renal or
hepatic impairment after administration of single and multiple doses. Eur J Clin Pharmacol,
1994, 46:41–47. Gammans RE, et al. Metabolism and disposition of buspirone. Am J Med,
1986, 80:41–51.
High: 949 ± 278
ng/mL b
References: Ehrsson H, et al. Busulfan kinetics. Clin Pharmacol Ther, 1983, 34:86–89.
Schuler US, et al. Pharmacokinetics of intravenous busulfan and evaluation of the bioavailability
of the oral formulation in conditioning for haematopoietic stem cell transplantation.
Bone Marrow Transplant, 1998, 22:241–244.
PO: ~61 <10% 99.9 0.43 ± 0.04 — 16.5 ± 3.1 b PO: 3-6 d IV: ~460 pg/mL d
IP: ~67 a Child c IP: 2-3 d PO: ~90 pg/mL d
a
Data from young (15-22 years) patients on peritoneal dialysis. Metabolized by 23-, 24-,
and 26-hydroxylases and also excreted into bile as its glucuronide. b Calcitriol t 1/2
is 5-8
hours in healthy adult subjects. c Oral dose t 1/2
= 27 ± 12 hours, children 2-16 years.
d
Following a single 60-ng/kg IV, intraperitoneal (IP) dialysate, or PO dose. Baseline plasma
levels were <10 pg/mL.
IP: ~105 pg/mL d
References: Jones CL, et al. Comparisons between oral and intraperitoneal 1,25-dihydroxyvitamin
D 3
therapy in children treated with peritoneal dialysis. Clin Nephrol, 1994, 42:44–49.
PDR54, 2000, p. 2650. Salusky IE, et al. Pharmacokinetics of calcitriol in continuous ambulatory
and cycling peritoneal dialysis patients. Am J Kidney Dis, 1990, 16:126–132.
Taylor CA, et al. Clinical pharmacokinetics during continuous ambulatory peritoneal dialysis.
Clin Pharmacokinet, 1996, 31:293–308.