Pharmacokinetics of gemcitabine combined with trastuzumab in patients with advanced breast cancer.
BACKGROUND
Combining the monoclonal antibody trastuzumab (TMAB) with chemotherapy is a new strategy in treatment of advanced breast cancer in HER+++ overexpressing patients.


METHODS
The disposition of gemcitabine has been investigated in 8 breast cancer patients (prospective cross-over design). Gemcitabine was administered as a 30-min i.v. infusion (1,000 mg/m(2) in 250 ml) on day 1 weekly for 3 weeks. On day 2 TMAB was infused with a loading dose of 4 mg/kg (90-min infusion) followed by a weekly maintenance dose of 2 mg/kg (30-min infusion). Pharmacokinetic analysis was performed after the first (= MONO) and after the third gemcitabine infusion (= TMAB).


RESULTS
Cmax was 22.2 microg/ml (t(max) = 24 min) in the MONO and 24.6 microg/ml (t(max) = 23 min) in the TMAB schedule. Gemcitabine distributed rapidly from plasma within a few minutes and was eliminated with a t1/2el of about 80 min in both arms of the study. The metabolite difluorodeoxyuridine (dFdU) appeared in plasma with t1/2appin = 12.8 min (MONO) or t1/2appin = 10.2 min (TMAB) reaching a mean peak concentration of 35.9 microg/ml (MONO) or 30.4 microg/ml (TMAB), respectively.


CONCLUSIONS
The results gave evidence that TMAB does not affect the disposition of gemcitabine.
Czejka
Martin
M
Department für Klinische Pharmazie und Diagnostik der Universität Wien, Austria. martin.czejka@univie.ac.at
Ostermann
Eva
E
Muric
Leila
L
Heinz
Doris
D
Schueller
Johannes
J
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D018592:Cross-Over Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D012720:Severity of Illness Index; D014018:Tissue Distribution / Q000187:drug effects; D000068878:Trastuzumab; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068878:Trastuzumab; D000093542:Gemcitabine