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Titolo:
Disposition of [G-H-3]paclitaxel and cremophor EL in a patient with severely impaired renal function
Autore:
Gelderblom, H; Verweij, E; Brouwer, E; Pillay, M; De Bruijn, P; Nooter, K; Stoter, G; Sparreboom, A;
Indirizzi:
Rotterdam Canc Inst, Daniel den Hoed Klin, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands Rotterdam Canc Inst Rotterdam Netherlands NL-3008 AE terdam, Netherlands Rotterdam Canc Inst, Daniel den Hoed Klin, Dept Nucl Med, NL-3008 AE Rotterdam, Netherlands Rotterdam Canc Inst Rotterdam Netherlands NL-3008 AE terdam, Netherlands Univ Rotterdam Hosp, NL-3008 AE Rotterdam, Netherlands Univ Rotterdam Hosp Rotterdam Netherlands NL-3008 AE terdam, Netherlands
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 11, volume: 27, anno: 1999,
pagine: 1300 - 1305
SICI:
0090-9556(199911)27:11<1300:DO[ACE>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
TAXOL METABOLISM; HUMAN PLASMA; NONLINEAR PHARMACOKINETICS; PACLITAXEL METABOLITES; LIQUID-CHROMATOGRAPHY; CYTOCHROME-P450 3A4; BIOLOGICAL-ACTIVITY; CANCER; 6-ALPHA-HYDROXYTAXOL; BIOTRANSFORMATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Sparreboom, A Rotterdam Canc Inst, Daniel den Hoed Klin, Dept Med Oncol, POB 5201, NL-3008 AE Rotterdam, Netherlands Rotterdam Canc Inst POB 5201 Rotterdam Netherlands NL-3008 AE
Citazione:
H. Gelderblom et al., "Disposition of [G-H-3]paclitaxel and cremophor EL in a patient with severely impaired renal function", DRUG META D, 27(11), 1999, pp. 1300-1305

Abstract

In the present work, we studied the pharmacokinetics and metabolic disposition of [G-H-3]paclitaxel in a female patient with recurrent ovarian cancerand severe renal impairment (creatinine clearance: similar to 20 ml/min) due to chronic hypertension and prior cisplatin treatment. During six 3-weekly courses of paclitaxel at a dose level of 157.5 mg/m(2) (viz. a 10% dose reduction), the renal function remained stable. Pharmacokinetic evaluation revealed a reproducible and surprisingly high paclitaxel area under the plasma concentration-time curve of 26.0 +/- 1.11 mu M.h (mean +/- S.D.; n = 6;c.v. = 4.29%), and a terminal disposition half-life of similar to 29 h. Both parameters are substantially increased (similar to 1.5-fold) when compared with kinetic data obtained from patients with normal renal function. Thecumulative urinary excretion of the parent drug was consistently low and averaged 1.58 +/- 0.417% (+/- S.D.) of the dose. Total fecal excretion (measured in one course) was 52.9% of the delivered radioactivity, and mainly comprised known mono- and dihydroxylated metabolites, with unchanged paclitaxel accounting for only 6.18%. The plasma area under the plasma concentration-time curve of the paclitaxel vehicle Cremophor EL, which can profoundly alter the kinetics of paclitaxel, was 114.9 +/- 5.39 mu l.h/ml, and not different from historic data in patients with normal or mild renal dysfunction. Urinary excretion of Cremophor EL was less than 0.1% of the total amount administered. These data indicate that the substantial increase in systemic exposure of the patient to paclitaxel relates to decreased renal metabolismand/or urinary elimination of polar radioactive species, most likely lacking an intact taxane ring fragment.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 12:22:49