2-Hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) is an alternative to alpha-, beta- and gamma-cyclodextrin, with improved water solubility and may be more toxicologically benign. This paper reviews the toxicity of HP-beta-CD, using both literature information and novel data, and presents new information. In addition, it includes a brief review from studies of the metabolism and pharmacokinetics of HP-beta-CD in both humans and animals. This review concludes that HP-beta-CD is well tolerated in the animal species tested (rats, mice and dogs), particularly when dosed orally, and shows only limited toxicity. In short duration studies, there were slight biochemical changes whereas studies of a longer duration, up to three months, produced additional minor haematological changes but no histopathological changes. When dosed intravenously, histopathological changes were seen in the lungs, liver and kidney but all findings were reversible and no effect levels were achieved. The carcinogenicity studies showed an increase in tumours in rats in the pancreas and intestines which are both considered to be rat-specific. There were also non-carcinogenic changes noted in the urinary tract, but these changes were also reversible and did not impair renal function. There were no effects on embryo-foetal development in either rats or rabbits. HP-beta-CD has been shown to be well tolerated in humans, with the main adverse event being diarrhoea and there have been no adverse events on kidney function, documented to date.
[1]
A. Hedges,et al.
Subchronic Toxicity of Orally Administered Beta-Cyclodextrin in Rats
,
1991
.
[2]
F. Hirayama,et al.
Improvement of chemical instability of digitoxin in aqueous solution by complexation with beta-cyclodextrin derivatives.
,
1988,
Chemical & pharmaceutical bulletin.
[3]
Joint Fao,et al.
Toxicological evaluation of certain food additives and contaminants
,
1987
.
[4]
A. C. Eissens,et al.
The Effect of Parenterally Administered Cyclodextrins on Cholesterol Levels in the Rat
,
2004,
Pharmaceutical Research.
[5]
M. Brewster,et al.
An intravenous toxicity study of 2-hydroxypropyl-β-cyclodextrin, a useful drug solubilizer, in rats and monkeys
,
1990
.
[6]
G. Schmid,et al.
Toxicological Comparison of Cyclodextrins
,
1996
.
[7]
D. Frank,et al.
Cyclodextrin nephrosis in the rat.
,
1976,
The American journal of pathology.
[8]
F. Hirayama,et al.
Cyclodextrin Drug Carrier Systems.
,
1998,
Chemical reviews.
[9]
T. G. Smith,et al.
β-Cyclodextrin : 52-week toxicity studies in the rat and dog
,
1995
.
[10]
K. Uekama,et al.
Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation.
,
1997,
Journal of pharmaceutical sciences.
[11]
J. Szejtli.
Introduction and General Overview of Cyclodextrin Chemistry.
,
1998,
Chemical reviews.