We have located links that may give you full text access.
CLINICAL TRIAL
CLINICAL TRIAL, PHASE I
COMPARATIVE STUDY
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL
Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors.
BACKGROUND: Vinorelbine is a vinca alkaloid obtained by hemisynthesis, which makes the molecule more lipophilic than the other vincas. An injectable formulation is already marketed for the treatment of non small cell lung cancer (NSCLC) and advanced breast cancer (ABC). A new oral form has been developed and its file registration is being submitted. As part of its development, a clinical study was conducted to determine the absolute bioavailability and pharmacokinetics of oral vinorelbine administered as softgel capsules, and to evaluate its safety profile compared with intravenous administration.
PATIENTS AND METHODS: Thirty-two patients with solid tumours were included in the study. Patients fasted and were randomised to receive vinorelbine on day 1, either as a 20 minute intravenous (i.v.) infusion of 25 mg/m2 or as softgel capsules at a dose of 80 mg/m2. Patients were treated with the alternate route after a one week wash-out period. Blood and urine samples for pharmacokinetic analysis were collected during each vinorelbine administration. Safety was assessed after each administration using the CALGB/expanded CTC classification.
RESULTS: Twenty-four patients were eligible for pharmacokinetic evaluation. Oral vinorelbine was rapidly absorbed at 80 mg/m2 (Tmax 1.4 +/- 0.7 h) and showed a bioavailability of 43 +/- 14, and close to 40% based on AUC(last) and AUC(inf), respectively. A bioequivalence analysis was conducted on dosage-normalised blood exposures. Equivalence was demonstrated between 80 mg/m2 oral and 30 mg/m2 i.v., and between 60 mg/m2 oral and 25 mg/m2 i.v. The inter-individual variability was equivalent for both routes (CV: 38% and 39% for oral and i.v., respectively). A correlation was found in both methods between AUClast and % nadir variation in white blood cells (WBC) and polymorphonuclears (PMN). More cases of neutropenia (all grades pooled), leucopenia (grades 3-4 only) and nausea (grades 2-3) were induced by 80 mg/m2 oral vinorelbine than by 25 mg/m2 i.v. The greatest intensity of these effects, following oral administration, probably reflects the higher, observed drug exposure.
CONCLUSION: At therapeutic dosage levels, pharmacokinetic behaviour and safety profiles were similar for both routes. The absolute bioavailability of the oral vinorelbine (new, soft gelatine capsule) was close to 40%. Inter-individual variability in drug exposure was equivalent in both routes. The pharmacokinetic/pharmacodynamic (PK/PD) relationship in haematological toxicity was independent of the routes of administration. Reliable, corresponding doses between oral and i.v. vinorelbine were established, which will result in bioequivalent AUC.
PATIENTS AND METHODS: Thirty-two patients with solid tumours were included in the study. Patients fasted and were randomised to receive vinorelbine on day 1, either as a 20 minute intravenous (i.v.) infusion of 25 mg/m2 or as softgel capsules at a dose of 80 mg/m2. Patients were treated with the alternate route after a one week wash-out period. Blood and urine samples for pharmacokinetic analysis were collected during each vinorelbine administration. Safety was assessed after each administration using the CALGB/expanded CTC classification.
RESULTS: Twenty-four patients were eligible for pharmacokinetic evaluation. Oral vinorelbine was rapidly absorbed at 80 mg/m2 (Tmax 1.4 +/- 0.7 h) and showed a bioavailability of 43 +/- 14, and close to 40% based on AUC(last) and AUC(inf), respectively. A bioequivalence analysis was conducted on dosage-normalised blood exposures. Equivalence was demonstrated between 80 mg/m2 oral and 30 mg/m2 i.v., and between 60 mg/m2 oral and 25 mg/m2 i.v. The inter-individual variability was equivalent for both routes (CV: 38% and 39% for oral and i.v., respectively). A correlation was found in both methods between AUClast and % nadir variation in white blood cells (WBC) and polymorphonuclears (PMN). More cases of neutropenia (all grades pooled), leucopenia (grades 3-4 only) and nausea (grades 2-3) were induced by 80 mg/m2 oral vinorelbine than by 25 mg/m2 i.v. The greatest intensity of these effects, following oral administration, probably reflects the higher, observed drug exposure.
CONCLUSION: At therapeutic dosage levels, pharmacokinetic behaviour and safety profiles were similar for both routes. The absolute bioavailability of the oral vinorelbine (new, soft gelatine capsule) was close to 40%. Inter-individual variability in drug exposure was equivalent in both routes. The pharmacokinetic/pharmacodynamic (PK/PD) relationship in haematological toxicity was independent of the routes of administration. Reliable, corresponding doses between oral and i.v. vinorelbine were established, which will result in bioequivalent AUC.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app