Comparative Pharmacokinetics and Biodistribution of Etoposide in a Polymer Dosage Form and as Free Drug Substance

• Published in: Pharmaceutical chemistry journal Vol. 52; no. 11; pp. 885 - 889
• Main Authors: Gukasova, N. V., Tubasheva, I. A., Kuznetsov, S. L., Murav’eva, A. I., Aleshin, S. V., Sokolov, V. V., Antipova, T. A., Vorontsov, E. A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 15-02-2019; Springer
• Subjects: Adenocarcinoma; Antineoplastic agents; Copolymers; Etoposide; Medicine; Organic Chemistry; Pharmacology/Toxicology; Pharmacy; Polymer industry; Polymers; Tumors; pharmacokinetics; biodistribution; etoposide; copolymer of lactic and glycolic acids; tissue availability
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-019-01921-4

A polymer dosage form of etoposide (PFE) was obtained as submicron particles based on the copolymer of lactic and glycolic acids (PLGA). Pharmacokinetics and biodistributions of etoposide in rat blood and organs after a single i.p. injection of the polymeric form and etoposide drug substance at doses of 10 mg/kg (of active ingredient) were compared and showed that absorption and elimination of etoposide from rat organs slowed if the PFE was used. The increases of
T
1/2
and
MRT
and decreases of
K
el
,
C
max
/
AUC
(0 – 48)
, and
Cl
were indicative of this. Liver and lungs had the greatest tissue availability (
f
t
) for the PFE. Etoposide accumulation in tumor tissue was studied after a single i.p. injection of PFE and etoposide drug substance at doses of 25 mg/kg to mice with grafted Ca755 murine breast adenocarcinoma. The etoposide distribution coefficient between blood and tumor tissue after 1 and 24 h was greater for the PFE, indicating the accumulation of etoposide in tumor tissue was greater if the PFE was used.