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

Lindnér, Per,1956Gothenburg University,Göteborgs universitet,Institutionen för de kirurgiska disciplinerna, Avdelningen för kirurgi,Institute of Surgical Sciences, Department of Surgery (författare)

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.

Heath, D D (författare)
Shalinsky, D R (författare)
Howell, S B (författare)
Naredi, Peter,1955Gothenburg University,Göteborgs universitet,Institutionen för de kirurgiska disciplinerna, Avdelningen för kirurgi,Institute of Surgical Sciences, Department of Surgery(Swepub:gu)xnarpe (författare)
Hafström, Lars-Olof,1936Gothenburg University,Göteborgs universitet,Institutionen för de kirurgiska disciplinerna, Avdelningen för kirurgi,Institute of Surgical Sciences, Department of Surgery(Swepub:gu)xhafla (författare)
Göteborgs universitetInstitutionen för de kirurgiska disciplinerna, Avdelningen för kirurgi (creator_code:org_t)

Av författaren/redakt...: Lindnér, Per, 19 ...; Heath, D D; Shalinsky, D R; Howell, S B; Naredi, Peter, 1 ...; Hafström, Lars-O ...

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