The effects of food on the pharmacokinetic profile of oral vinorelbine

Abstract

The effects of food on the pharmacokinetics and safety profile of a soft-gel capsule formulation of vinorelbine (Navelbine Oral) were evaluated in fed and fasted patients with solid tumours or lymphomas. A group of 18 patients (12 planned) were entered into a multicentre phase I pharmacokinetic study following a crossover design with a 1-week wash-out period. Patients received the first dose of 80 mg/m(2) oral vinorelbine either after fasting or after ingestion of a standard continental breakfast. The second dose of 80 mg/m(2) was administered 1 week later in the alternate feeding condition to the first dose. Of the 18 patients, 13 were eligible for pharmacokinetic evaluation. The mean time to maximum concentration (T(max)) was shorter in fasted patients (1.63+/-0.98 h in blood, 1.67+/-0.96 h in plasma) than in fed patients (2.48+/-1.40 h in blood, 2.56+/-1.65 h in plasma) but these differences are not likely to modify the safety and/or efficacy of oral vinorelbine. Values for C(max) and AUC were similar in fed and fasted patients and no significant differences were observed. The safety profile of oral vinorelbine observed in this limited number of patients appears to be comparable to that usually reported for vinorelbine, the main toxicity being neutropenia. Only one episode of febrile neutropenia was reported. The main nonhaematological toxicities encountered were gastrointestinal, consisting of nausea, vomiting, diarrhoea and constipation. A tendency for a lower incidence of vomiting was suggested when oral vinorelbine was administered after a standard breakfast. Based on this study, the administration of oral vinorelbine to fasted patients is not mandatory since administration after a standard breakfast does not lead to differences in body exposure to the drug. As the comfort of patients may be improved when the treatment is administered after a light meal, this procedure can be recommended in clinical practice.

Metabolism pathway of vinorelbine (Navelbine®) in human: Characterisation of the metabolites by HPLC–MS/MS

“…3 and Table 1), therefore confirming the clinical findings on plasma and blood [5,12,13]. Enzymatic oxidation was highly suspected to be involved in the biotransformation of VRL to M2 as reported for vindoline or vinblastine [18].…”

“…Thanks to a new, highly sensitive HPLC method [5], DVRL was quantified for the first time in blood whatever the route of administration, and its pharmacokinetics was largely discussed [11][12][13]. Knowledge of the metabolism pathway is a key issue in the development of an oral form since some metabolites can be generated in the gastro-intestinal tract.…”

A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine

“…Food intake induced an increase in the time lag from 10 to about 30 min, but the absorption rate constant and bioavailability factor were not affected. As the value of lag-time (less than 1 h) is low compared with the dosing schedule (weekly administration), no specific recommendation seems necessary when oral vinorelbine is taken with food, as previously suggested by Bugat et al [22]. The rapid absorption process (t 1/2 absorption=1.4 h) of vinorelbine should prevent drug loss in the case of vomiting.…”

Oral Vinorelbine and Cisplatin with Concomitant Radiotherapy in Stage III Non-Small Cell Lung Cancer (NSCLC): A Feasibility Study

“…Cisplatin/vinorelbine was thought to show the most favorable efficacy/toxicity profile [12]. Vinorelbine is available in oral as well as intravenous form, with proven efficacy in NSCLC [13] and stable absorption from the digestive tract [14]. The administration of oral chemotherapy concurrent with radiotherapy is attractive in an outpatient setting, but the dose for oral vinorelbine in combination with cisplatin and concurrent chemoradiotherapy is not yet established.…”