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Regional lymphatic drug exposure following intraperitoneal administration of 5-fluorouracil, carboplatin, and etoposide.

Artikel i vetenskaplig tidskrift
Författare Per Lindnér
D D Heath
D R Shalinsky
S B Howell
Peter Naredi
Lars-Olof Hafström
Publicerad i Surgical oncology
Volym 2
Nummer/häfte 2
Sidor 105-12
ISSN 0960-7404
Publiceringsår 1993
Publicerad vid Institutionen för de kirurgiska disciplinerna, Avdelningen för kirurgi
Sidor 105-12
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Animals, Ascitic Fluid, chemistry, Carboplatin, administration & dosage, pharmacokinetics, Etoposide, administration & dosage, pharmacokinetics, Fluorouracil, administration & dosage, pharmacokinetics, Half-Life, Injections, Intraperitoneal, Lymph, chemistry, Lymph Nodes, chemistry, Peritoneum, metabolism, Permeability, Swine
Ämneskategorier Cancer och onkologi

Sammanfattning

Intraperitoneal (i.p.) administration of chemoterapeutic agents results in greater total drug exposures in the peritoneal cavity than in plasma. A study on the drug exposure for i.p. lymphatics of pigs, receiving 5-fluorouracil (5-FU), etoposide (VP-16) and carboplatin (CBDCA) by the i.p. route was conducted. Drug concentrations in peritoneal fluid, plasma, and thoracic duct lymph were monitored over the ensuing 3 h. 5-FU appeared rapidly in thoracic duct, lymph and plasma. The lymph concentration declined after 20 min while the plasma concentration remained stable. CBDCA reached a stable concentration in lymph and plasma after 60 min. VP-16 peaked in the lymph after 20 min, whereas the plasma concentration continued to rise for 150 min; the peritoneal half-life for VP-16 was too long for clearance to be defined. Total drug exposure (AUC) was for 5-FU 5.7-fold greater for lymph than for plasma and for CBDCA equal in both compartments. VP-16 had a 2.1-fold higher AUC for lymph than for plasma. The results indicate that the i.p. route of administration results in a greater exposure of the lower thoracic duct lymph than the plasma to 5-FU, produces only a marginally increased exposure to VP-16, and results in no difference for CBDCA. The efficacy of 5-FU is a function of total drug exposure. The results reported provide a strong rationale for evaluating the adjuvant use of i.p. 5-FU in colorectal and gastric carcinoma.

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