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
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
The Effect of Parenterally Administered Cyclodextrins on the Pharmacokinetics of Coadministered Drugs
چکیده انگلیسی
Cyclodextrins are used increasingly to formulate otherwise poorly soluble molecules for clinical use. Cyclodextrins, such as 2-hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether ß-cyclodextrin (SBEßCD), are found in marketed parenteral drug formulations. Depending upon the relative affinities of a coadministered medication for cyclodextrin and plasma proteins, complexation with HPßCD or SBEßCD may alter its pharmacokinetics (PK). To explore this possibility, we applied a previously developed model for competitive binding of drugs with HPßCD 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 HPßCD complexation with their therapeutic action (e.g., antibiotics), supplemented by a composite listing of concurrent medications. Stability constant (K1:1) values for drug-HPßCD 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 40,000 M- 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 HPßCD 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
نویسندگان
, , , ,