کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485633 | 1114362 | 2012 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Effect of Parenterally Administered Cyclodextrins on the Pharmacokinetics of Coadministered Drugs
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Cyclodextrins are used increasingly to formulate otherwise poorly soluble molecules for clinical use. Cyclodextrins, such as 2-hydroxypropyl-Ã-cyclodextrin (HPÃCD) and sulfobutylether Ã-cyclodextrin (SBEÃCD), are found in marketed parenteral drug formulations. Depending upon the relative affinities of a coadministered medication for cyclodextrin and plasma proteins, complexation with HPÃCD or SBEÃCD may alter its pharmacokinetics (PK). To explore this possibility, we applied a previously developed model for competitive binding of drugs with HPÃCD and human serum albumin to a variety of commonly administered medications. We modeled this potential interaction in medications chosen on the basis of a hypothetical detrimental effect of HPÃCD complexation with their therapeutic action (e.g., antibiotics), supplemented by a composite listing of concurrent medications. Stability constant (K1:1) values for drug-HPÃCD 1:1 inclusion complexes were extracted from our own data and the literature. The K1:1 values for the drugs tested ranged from 2 to 40,000Â M-Â 1 and the plasma protein binding from about 20% to over 99%. None of the 63 drugs examined in the present study had a sufficiently high K1:1 value for HPÃCD complexation to affect plasma protein binding to a degree that would be expected to alter their PK substantively, for example, to require increased doses.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 12, December 2012, Pages 4402-4408
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 12, December 2012, Pages 4402-4408
نویسندگان
Sergey V. Kurkov, Donna E. Madden, Daniel Carr, Thorsteinn Loftsson,