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

Pramlintide a
30-40% b – ~60 c Low: 14.9 ± 3.9 d 0.43 IV: 0.4-0.75 0.32-0.35 f Low: 21 ± 3 pmol/L f
High: 14.5 ± 4.0 d 0.71 SC: 0.5-0.83 High: 77 ± 22 pmol/L f
i RD e
a
Pramlintide is a synthetic peptide analog of amylin for the treatment of both type 1 and
type 2 diabetes. It is metabolized in the kidneys to at least one primary active metabolite:
Des-lys(1)pramlintide (2-37 pramlintide) with a t 1/2
similar to that of the parent drug. b SC
administration with greater variability in response when the injection is into the arm compared
to into the abdomen or thigh. c Not extensively bound to blood cells or albumin. d Based
on IV infusion of a low dose of 30 μg for type 1 diabetes and a high dose of 100 μg for type 2
diabetes. e Study in patients with moderate to severe renal impairment. No data in end-stage
RD. f Following a low SC dose of 30 μg and a high SC dose of 100 μg.
Pravastatin
18 ± 8 47 ± 7 43-48 13.5 ± 2.4 0.46 ± 0.04 0.8 ± 0.2 b 1-1.4 c 28-38 ng/mL c
b LD
i Aged, RD a
i Aged, RD a
a
Although renal CL decreases with reduced renal function, no significant changes in CL/F or
t 1/2
are seen following oral dosing as a result of the low and highly variable bioavailability. b A
longer t 1/2
= 1.8 ± 0.8 hour reported for oral dosing; probably rate limited by absorption.
c
Range of mean values from different studies following a single 20-mg oral dose.
Praziquantel a
References: Colburn WA, et al. Pharmacokinetics and pharmacodynamics of AC137 (25,28,29
triproamylin, human) after intravenous bolus and infusion doses in patients with insulindependent
diabetes. J Clin Pharmacol, 1996, 36:13–24. Drugs@FDA. Symlin label approved
on 9/25/07. Available at: http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/. Accessed
on August 1, 2009. Kolterman OG, et al. Effect of 14 days’ subcutaneous administration of
the human amylin analogue, pramlintide (AC137), on an intravenous insulin challenge and
response to a standard liquid meal in patients with IDDM. Diabetologia, 1996, 39:492–499.
References: Corsini A, et al. New insights into the pharmacodynamic and pharmacokinetic
properties of statins. Pharmacol Ther, 1999, 84:413–428. Desager JP, et al. Clinical pharmacokinetics
of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. Clin
Pharmacokinet, 1996, 31:348–371. Quion JA, et al. Clinical pharmacokinetics of pravastatin.
Clin Pharmacokinet, 1994, 27:94–103.
— b Negligible 80-85 5 mg/kg: 467 c 50 mg/kg: 5 mg/kg: 1.5-1.8 e 0.8-6.3 μg/L e
9.55 ± 2.86 0.8-1.5 c
40-60 mg/kg: 40-60 mg/kg:
57-222 c 1.7-3.0 c
b LD d
a LD
a
Data from male and female patients with schistosomiasis. b Absolute bioavailability is not
known. Praziquantel is well absorbed (80%) but undergoes significant first-pass metabolism
(hydroxylation), the extent of which appears to be dose dependent. c CL/F and V ss
/F reported;
CL/F and t 1/2
are dose dependent. d CL/F reduced, moderate to severe hepatic impairment.
e
Range of mean values from different studies following a single 40- to 60-mg/kg oral dose.
References: Edwards G, et al. Clinical pharmacokinetics of anthelmintic drugs. Clin
Pharmacokinet, 1988, 15:67–93. el Guiniady MA, et al. Clinical and pharmacokinetic study
of praziquantel in Egyptian schistosomiasis patients with and without liver cell failure. Am J
Trop Med Hyg, 1994, 51:809–818. Jung H, et al. Clinical pharmacokinetics of praziquantel.
Proc West Pharmacol Soc, 1991, 34:335–340. Sotelo J, et al. Pharmacokinetic optimisation of
the treatment of neurocysticercosis. Clin Pharmacokinet, 1998, 34:503–515. Watt G, et al.
Praziquantel pharmacokinetics and side effects in Schistosoma japonicum-infected patients
with liver disease. J Infect Dis, 1988, 157:530–535.
(Continued)
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
1965