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Titolo:
Plasma and cerebrospinal fluid pharmacokinetics of gemcitabine after intravenous administration in nonhuman primates
Autore:
Kerr, JZ; Berg, SL; Dauser, R; Nuchtern, J; Egorin, MJ; McGuffey, A; Aleksic, A; Blaney, S;
Indirizzi:
Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 rens Canc Ctr, Houston, TX 77030 USA Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 ept Neurosurg, Houston, TX 77030 USA Baylor Coll Med, Dept Surg, Houston, TX 77030 USA Baylor Coll Med HoustonTX USA 77030 ed, Dept Surg, Houston, TX 77030 USA Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 st Canc, Pittsburgh, PA 15213 USA
Titolo Testata:
CANCER CHEMOTHERAPY AND PHARMACOLOGY
fascicolo: 5, volume: 47, anno: 2001,
pagine: 411 - 414
SICI:
0344-5704(200105)47:5<411:PACFPO>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
METASTATIC BREAST-CANCER; CELL LUNG-CANCER; PHASE-II TRIAL; PHARMACOLOGY; METABOLISM; LEUKEMIA; INFUSION;
Keywords:
gemcitabine; nonhuman primates; plasma pharmacokinetics; cerebrospinal fluid pharmacokinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Blaney, S Baylor Coll Med, Texas Childrens Canc Ctr, 6621 Fannin St, Houston, TX 77030 USA Baylor Coll Med 6621 Fannin St Houston TX USA 77030 TX 77030 USA
Citazione:
J.Z. Kerr et al., "Plasma and cerebrospinal fluid pharmacokinetics of gemcitabine after intravenous administration in nonhuman primates", CANC CHEMOT, 47(5), 2001, pp. 411-414

Abstract

Purpose: Gemcitabine (dFdC) is a difluorine-substituted deoxycytidine analogue that has demonstrated antitumor activity against both leukemias and solid tumors. Pharmacokinetic studies of gemcitabine have been performed in both adults and children but to date there have been no detailed studies of its penetration into cerebrospinal fluid (CSF). The current study was performed in nonhuman primates to determine the plasma and CSF pharmacokinetics of gemcitabine and its inactive metabolite, difluorodeoxyuridine (dFdU) following i.v. administration. Methods. Gemcitabine, 200 mg/kg, was administered i.v. over 45 min to four nonhuman primates. Serial plasma and CSF samples were obtained prior to, during, and after completion of the infusion for determination of gemcitabine and dFdU concentrations. Gemcitabine and dFdU concentrations were measured using high-performance liquid chromatography (HPLC) and modeled with model-dependent and model-independent methods. Results. Plasma elimination was rapid with a mean t(1/2) of 8 +/- 4 min (mean +/- SD) for gemcitabine and 83 +/- 8 min for dFdU. Gemcitabine total body clearance (Cl-TB) was 177 +/- 40 ml/min per kg and the Vd(ss) was 5.5 +/- 1.0 l/kg. The maximum concentrations (C-max) and areas under the time concentration curves (AUC) for gemcitabine and dFdU in plasma were 194 +/- 64 muM and 63.8 +/- 14.6 muM.h, and 783 +/- 99 muM and 1725 +/- 186 muM.h, respectively. The peak CSF concentrations of gemcitabine and dFdU were 2.5 +/-1.4 muM and 32 +/- 41 muM, respectively. The mean CSF:plasma ratio was 6.7% for gemcitabine and 23.8% for dFdU. Conclusions. There is only modest penetration of gemcitabine into the CSF after i.v. administration. The relatively lowCSF exposure to gemcitabine after i.v. administration suggests that systemic administration of this agent is not optimal for the treatment of overt leptomeningeal disease. However, the clinical spectrum of antitumor activityand lack of neurotoxicity after systemic administration of gemcitabine make this agent an excellent candidate for further studies to assess the safety and feasibility of intrathecal administration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 06:24:36