![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
PA Cossum, L Truong, SR Owens, PM Markham, JP Shea and ST Crooke
Triplex Pharmaceuticals Corporation, The Woodlands, Texas.
After intradermal administration of 3.7 mg/kg of 14C-labeled 5'- TTGCTTCCATCTTCCTCGTC-3' (14C-labeled ISIS 2105) to rats, a phosphorothioate oligodeoxynucleotide, absorption was rapid. Approximately 65% of the administered dose was absorbed within 1 hr after the dose and peak blood levels were achieved within 30 min. After the initial rapid phase of absorption, a slower absorption phase ensued that resulted in more than 95% of the dose being cleared from the injection site. Slow metabolism of 14C-labeled ISIS 2105 occurred at the injection site. The rate and characteristics of metabolism in the skin were similar to those observed in other tissues. Once absorbed, the pharmacokinetics, distribution and metabolism of 14C-labeled ISIS 2105 after intradermal administration were comparable to those after an i.v. dose. The distribution and terminal half-lives were 0.5 and 53 hr, respectively. Levels of 14C-labeled ISIS 2105 in the blood were found in the plasma and the drug distributed broadly to all peripheral tissues; the liver, renal cortex and bone marrow accumulated the highest levels of drug. The 14C-labeled ISIS 2105 was eliminated principally by metabolism. Approximately 50% of the dose was found in expired air and 15% and 5% were found in urine and feces, respectively. No intact oligonucleotide was found in urine or feces at any time.
This article has been cited by other articles:
|
|
 |
|
  S. M. O'Brien, C. C. Cunningham, A. K. Golenkov, A. G. Turkina, S. C. Novick, and K. R. Rai Phase I to II Multicenter Study of Oblimersen Sodium, a Bcl-2 Antisense Oligonucleotide, in Patients With Advanced Chronic Lymphocytic Leukemia J. Clin. Oncol., October 20, 2005; 23(30): 7697 - 7702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Henry, D.K. Monteith, J.E. Matson, B.H. Mathison, K.S. Loveday, R.A. Winegar, J.E. Matson, P.S. Lee, E.S. Riccio, J.P. Bakke, et al. Assessment of the genotoxic potential of ISIS 2302: a phosphorothioate oligodeoxynucleotide Mutagenesis, May 1, 2002; 17(3): 201 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Geary, O. Khatsenko, K. Bunker, R. Crooke, M. Moore, T. Burckin, L. Truong, H. Sasmor, and A. A. Levin Absolute Bioavailability of 2'-O-(2-Methoxyethyl)-Modified Antisense Oligonucleotides following Intraduodenal Instillation in Rats J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 898 - 904. [Abstract] [Full Text]
|
|
|
|
|
|
M. Butler, R. M. Crooke, M. J. Graham, K. M. Lemonidis, M. Lougheed, S. F. Murray, D. Witchell, U. Steinbrecher, and C. F. Bennett Phosphorothioate Oligodeoxynucleotides Distribute Similarly in Class A Scavenger Receptor Knockout and Wild-Type Mice J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 489 - 496. [Abstract] [Full Text]
|
|
|
|
|
|
J. Nemunaitis, J. T. Holmlund, M. Kraynak, D. Richards, J. Bruce, N. Ognoskie, T. J. Kwoh, R. Geary, A. Dorr, D. Von Hoff, et al. Phase I Evaluation of ISIS 3521, an Antisense Oligodeoxynucleotide to Protein Kinase C-Alpha, in Patients With Advanced Cancer J. Clin. Oncol., November 1, 1999; 17(11): 3586 - 3595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Monteith, M. J. Horner, N. A. Gillett, M. Butler, R. Geary, T. Burckin, T. Ushiro-Watanabe, and A. A. Levin Evaluation of the Renal Effects of an Antisense Phosphorothioate Oligodeoxynucleotide in Monkeys Toxicol Pathol, May 1, 1999; 27(3): 307 - 317. [Abstract] [PDF]
|
|
|
|
|
|
S. P. Henry, M. V. Templin, N. Gillett, J. Rojko, and A. A. Levin Correlation of Toxicity and Pharmacokinetic Properties of a Phosphorothioate Oligonucleotide Designed to Inhibit ICAM-1 Toxicol Pathol, January 1, 1999; 27(1): 95 - 100. [Abstract] [PDF]
|
|
|
|
 |
|
 R. S. Geary, J. M. Leeds, J. Fitchett, T. Burckin, L. Truong, C. Spainhour, M. Creek, and A. A. Levin Pharmacokinetics and Metabolism in Mice of a Phosphorothioate Oligonucleotide Antisense Inhibitor of C-raf-1 Kinase Expression Drug Metab. Dispos., November 1, 1997; 25(11): 1272 - 1281. [Abstract] [Full Text]
|
|
|
|
|
|
J. M. Glover, J. M. Leeds, T. G. K. Mant, D. Amin, D. L. Kisner, J. E. Zuckerman, R. S. Geary, A. A. Levin, and W. R. Shanahan Jr. Phase I Safety and Pharmacokinetic Profile of an Intercellular Adhesion Molecule-1 Antisense Oligodeoxynucleotide (ISIS 2302) J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1173 - 1180. [Abstract] [Full Text]
|
|
|
|
|
|
J. M. Leeds, S. P. Henry, L. Truong, A. Zutshi, A. A. Levin, and D. Kornbrust Pharmacokinetics of a Potential Human Cytomegalovirus Therapeutic, a Phosphorothioate Oligonucleotide, After Intravitreal Injection in the Rabbit Drug Metab. Dispos., August 1, 1997; 25(8): 921 - 926. [Abstract] [Full Text]
|
|
|
|
|
|
T. L. Wallace, S. A. Bazemore, K. Holm, P. M. Markham, J. P. Shea, N. Chaudhary, and P. A. Cossum Pharmacokinetics and Distribution of a 33P-labeled Anti-Human Immunodeficiency Virus Oligonucleotide (AR177) after Single- and Multiple-Dose Intravenous Administration to Rats J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1480 - 1488. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
