Pharmacokinetics of docetaxel during hyperthermic intraperitoneal chemotherapy for peritoneal metastasis.
The purpose of this manuscript is to report the pharmacokinetics of docetaxel during hyperthermic intraperitoneal chemotherapy (HIPEC) after peritonectomy.


METHODS
Eleven patients with peritoneal metastasis (PM) underwent peritonectomies combined with 40 min of HIPEC with 40 mg/body of docetaxel. The pharmacokinetics of docetaxel were studied by using high-performance liquid chromatography.


RESULTS
The docetaxel concentration at the start of HIPEC (0 min) was 9.084 ± 0.972 mg/L. The concentration gradually decreased to 5.599 ± 0.458 mg/L 40 min after HIPEC. In contrast, serum docetaxel levels increased during HIPEC, reaching a maximum level of 0.1334 ± 0.0726 mg/L at 40 min. The clearance (CLp) was 3.164 ± 1.383 L/hr, and the area under the curve (AUC) ratio was 95.12 ± 87.32. The AUC ratio of less-extensive peritonectomies was significantly higher than that of extended peritonectomies. The docetaxel concentration in the tumor tissue increased at 40 min (4.45 mg/gr). The apparent permeability (Papp, 40 min) was 1.47 ± 0.67 mm/40 min. No severe adverse effects were observed after HIPEC.


CONCLUSIONS
From these results, 40 mg is a safe dose for docetaxel combined with HIPEC, and the locoregional intensity of docetaxel is enough to control PM less than 1.47 mm in diameter.
NPO Organization to Support Peritoneal Surface Malignancy Treatment.
Yutaka
Y
Yonemura
Emel
E
Canbay
Shouzou
S
Sako
Haruaki
H
Ishibashi
Masamitu
M
Hirano
Akiyoshi
A
Mizumoto
Kazuyosi
K
Takeshita
Nobuyuki
N
Takao
Masumi
M
Ichinose
Yang
Y
Liu
Yan
Y
Li
Satoshi
S
Ikeda
Ayaka
A
Noguchi
Yoshimichi
Y
Sai
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D043823:Taxoids / Q000493:pharmacokinetics*; D055815:Young Adult
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel