Pharmacokinetics and Biodistribution of Anastrozole in a Polymer-Containing Formulation

• Published in: Pharmaceutical chemistry journal Vol. 53; no. 10; pp. 883 - 889
• Main Authors: Gukasova, N. V., Tubasheva, I. A., Kuznetsov, S. L., Aleshin, S. V., Sokolov, V. V., Antipova, T. A., Poltavets, Yu. I., Krasheninnikova, A. A., Vorontsov, E. A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2020; Springer
• Subjects: International economic relations; Medicine; Molecular Biological Problems of Drug Design and Mechanism of Drug Action; Organic Chemistry; Pharmacology/Toxicology; Pharmacy; Polymer industry; pharmacokinetics; biodistribution; aromatase; anastrozole; copolymer of lactic and glycolic acids; tissue availability
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-020-02094-1

A polymer-containing anastrozole formulation (PAF) in the form of micronized particles based on a copolymer of lactic and glycolic acids with a terminal carboxyl group (PLGA-COOH 50/50) was prepared. The pharmacokinetics and biodistribution of anastrozole in the organs of rats after single intramuscular (i.m.) doses of PAF and anastrozole substance 6.8 mg/kg (in terms of active substance) were studied. The pharmacokinetics of anastrozole were found to be linear over the range 1.7 – 6.8 mg/kg, in terms of
AUC
(0 – 336)
(
R
2
= 0.99989) and
C
max
(
R
2 = 0.99767) after i.m. administration of the PAF developed here to rats. Use of PAF was found to slow the absorption and elimination of anastrozole in the blood, liver, kidneys, bone, adrenals, fatty tissue, and muscles in rats, as evidenced by increases in the
T
1/2
and
MRT
and decreases in
Cl
,
K
el
, and
C
max
/
AUC
(0 – 336)
. Tissue availability of anastrozole (
f
T
) in the adrenals, fatty tissue, and muscles of rats after administration as PAF was 1.12, 1.44, and 1.37 times higher respectively than after administration of anastrozole substance.