HUMAN DRUG CLEARANCE;
OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE GEM-91;
MODIFIED ANTISENSE OLIGONUCLEOTIDE;
NECROSIS-FACTOR-ALPHA;
PHASE-I TRIAL;
INTRAVENOUS-INFUSION;
PREDICTION;
HUMANS;
BCL-2;
METABOLISM;
D O I:
10.1089/nat.2011.0299
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The objective of this study was to evaluate the predictive performance of interspecies scaling of oligonucleotides to predict clearance and volume of distribution at steady state in humans from animal data. The human pharmacokinetic parameters were predicted using 1, 2, or at least 3 animal species. The results of the study indicated that the pharmacokinetic parameters of oligonucleotides can be predicted with reasonable accuracy in humans when at least 3 animal species are employed. On the other hand, allometric scaling based on 1 or 2 species or fixed coefficient or fixed exponent can be erratic and unreliable. Further work should be conducted in this direction.
机构:
Leiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, NetherlandsLeiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, Netherlands
Calvier, Elisa A. M.
Krekels, Elke H. J.
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机构:
Leiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, NetherlandsLeiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, Netherlands
Krekels, Elke H. J.
Valitalo, Pyry A. J.
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机构:
Leiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, NetherlandsLeiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, Netherlands
Valitalo, Pyry A. J.
Rostami-Hodjegan, Amin
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机构:
Univ Manchester, Manchester Pharm Sch, Manchester, Lancs, EnglandLeiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, Netherlands
Rostami-Hodjegan, Amin
Tibboel, Dick
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机构:
Erasmus Univ, Sophia Childrens Hosp, Med Ctr, Intens Care & Dept Pediat Surg, Rotterdam, NetherlandsLeiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, Netherlands
Tibboel, Dick
Danhof, Meindert
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机构:
Leiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, NetherlandsLeiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, Netherlands
Danhof, Meindert
Knibbe, Catherijne A. J.
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机构:
Leiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, Netherlands
St Antonius Hosp, Dept Clin Pharm, Nieuwegein, NetherlandsLeiden Univ, LACDR, Div Pharmacol, NL-2333 CC Leiden, Netherlands
机构:
Univ Melbourne, Royal Bot Gardens, Australian Res Ctr Urban Ecol, Melbourne, Vic 3010, AustraliaUniv Melbourne, Royal Bot Gardens, Australian Res Ctr Urban Ecol, Melbourne, Vic 3010, Australia
McCarthy, Michael A.
Citroen, Rebecca
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机构:Univ Melbourne, Royal Bot Gardens, Australian Res Ctr Urban Ecol, Melbourne, Vic 3010, Australia
Citroen, Rebecca
McCall, Sarah C.
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机构:Univ Melbourne, Royal Bot Gardens, Australian Res Ctr Urban Ecol, Melbourne, Vic 3010, Australia
机构:
Yeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, 144 Coll St, Toronto, ON M5S 3M2, CanadaYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
Noh, Keumhan
Kang, Wonku
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机构:
Chung Ang Univ, Coll Pharm, Seoul 06974, South KoreaYeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea