OBJECTIVE: To investigate a possible pharmacokinetic interaction between gemcitabine (GEM) and vinorelbine (VNR), when co-administered following the alternate sequences GEM-VNR and VNR-GEM. METHODS: Enrolled in this study were 31 patients with different advanced carcinoma: 9 patients were given GEM (1 h i.v. infusion, 1000 mg/m2) followed after 5 min by VNR (10 min i.v. infusion, 25 mg/m2) (GEM-VNR sequence); 17 patients received VNR followed by GEM (VNR-GEM sequence), at the same doses and with the same infusion period; as a control group (GEM), 5 patients were given only single-agent gemcitabine (1 h i.v. infusion, 1000 mg/m2). RESULTS: GEM serum levels showed higher Cmax and AUC(tot) in the VNR-GEM protocol than in the GEM-VNR and GEM groups. The GEM pharmacokinetic profile in both schedules showed biphasic elimination, as in monotherapy. VNR concentration/time curves showed rapid plasma clearance and wide interpatient variability in both sequences. VNR Cmax was higher in the VNR-GEM group than in GEM-VNR, while VNR AUC(tot) and Cl(tot) did not differ significantly in the two sequences. CONCLUSIONS: Some pk-values were altered for both GEM and VNR, following the two alternate protocols. A possible rationale for this behaviour is that VNR and GEM may influence each other during liver elimination extraction and metabolism.
OBJECTIVE: To investigate a possible pharmacokinetic interaction between gemcitabine (GEM) and vinorelbine (VNR), when co-administered following the alternate sequences GEM-VNR and VNR-GEM. METHODS: Enrolled in this study were 31 patients with different advanced carcinoma: 9 patients were given GEM (1 h i.v. infusion, 1000 mg/m2) followed after 5 min by VNR (10 min i.v. infusion, 25 mg/m2) (GEM-VNR sequence); 17 patients received VNR followed by GEM (VNR-GEM sequence), at the same doses and with the same infusion period; as a control group (GEM), 5 patients were given only single-agent gemcitabine (1 h i.v. infusion, 1000 mg/m2). RESULTS:GEM serum levels showed higher Cmax and AUC(tot) in the VNR-GEM protocol than in the GEM-VNR and GEM groups. The GEM pharmacokinetic profile in both schedules showed biphasic elimination, as in monotherapy. VNR concentration/time curves showed rapid plasma clearance and wide interpatient variability in both sequences. VNR Cmax was higher in the VNR-GEM group than in GEM-VNR, while VNR AUC(tot) and Cl(tot) did not differ significantly in the two sequences. CONCLUSIONS: Some pk-values were altered for both GEM and VNR, following the two alternate protocols. A possible rationale for this behaviour is that VNR and GEM may influence each other during liver elimination extraction and metabolism.
Authors: R Sorio; I Robieux; E Galligioni; A Freschi; A M Colussi; D Crivellari; S Saracchini; S Monfardini Journal: Eur J Cancer Date: 1997-02 Impact factor: 9.162
Authors: G Pérez-Manga; A Lluch; E Alba; J A Moreno-Nogueira; M Palomero; J García-Conde; D Khayat; N Rivelles Journal: J Clin Oncol Date: 2000-07 Impact factor: 44.544