Liver Diseases
Conditions
Keywords
Paclitaxel, Pharmacokinetics, Egypt
Brief summary
The study aims to assess the pharmacokinetics of paclitaxel and its two major metabolites in patients with normal and impaired liver functions.
Detailed description
population pharmacokinetic study in patients with normal or impaired liver functions, receiving paclitaxel for cancer treatment. 40 Patients with histologically confirmed solid tumors will be enrolled in the study: * 20 patients have normal liver functions as defined by transaminase \< 2.6 x ULN and bilirubin values \< 1.26 x ULN. * 20 patients with liver impairment as defined by transaminase 2.6 - 10 x ULN and bilirubin values 1.26 - 5 x ULN.
Interventions
OTHERBlood samples
Plasma concentrations of paclitaxel and its metabolites will be obtained during the first treatment cycle. The samples for paclitaxel analysis will be collected in ethylenediamine tetraacetic acid tubes at 7-time points: just before infusion, in the middle of the infusion, at the end of infusion, at 1, 2, 4 and 6 hours post-infusion.
Sponsors
Ain Shams University
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with histologically proven non haematopoietic malignancy (ovarian, breast and lung cancer). * Age between 18 and 70 years * At least a 4-week interval between the last dose of previous chemotherapy protocol and registration (6 weeks in case of treatment with carboplatin). * Glomerular filtration rate \> 60 ml/min * An Eastern Cooperative Oncology Group performance status 0-2, a life expectancy of \> 12 weeks, adequate bone marrow function \[absolute neutrophil count (ANC) ≥ 1 X 109 and platelets ≥ 100 X 109\] * Patient accessible for treatment and follow-up and written informed consent.
Exclusion criteria
* Prior treatment with paclitaxel or other taxanes. * Pre-existing motor or sensory neurotoxicity \> grade 2 according to World Health Organization (WHO) criteria. * Active infection or other serious underlying medical condition (including prior allergic reactions to Paclitaxel or the drug's constituents), dementia or significantly altered mental status, symptomatic brain or liver metastases, history of atrial or ventricular arrhythmias or congestive heart failure even if medically controlled, history of clinical and electrocardiographically documented myocardial infarction. * Simultaneous use of any medication, dietary supplements, or other compounds known to inhibit affect the pharmacokinetics of paclitaxel. * Patients with difficult blood sampling.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| plasma concentrations of paclitaxel | predose till 6 hours post infusion of paclitaxel | determination of plasma concentration and pharmacokinetic analysis of paclitaxel |
| plasma concentrations of 6-α-hydroxypaclitaxel | predose till 6 hours post infusion of paclitaxel | determination of plasma concentration and pharmacokinetic analysis of 6-α-hydroxypaclitaxel |
| plasma concentrations of 3'-p-hydroxypaclitaxel | predose till 6 hours post infusion of paclitaxel | determination of plasma concentration and pharmacokinetic analysis of 3'-p-hydroxypaclitaxel |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Probing CYP 3A4 activity | predose till 6 hours post infusion of paclitaxel | metabolite ratio of 6-α-hydroxypaclitaxel/paclitaxel |
| Probing CYP 2C8 activity | predose till 6 hours post infusion of paclitaxel | metabolite ratio of 3'-p-hydroxypaclitaxel/paclitaxel |
| Incidence of adverse effects | baseline ( before first dose) till 100 days after the first dose | Complete blood count, liver functions and neuropathy evaluation (according to Common Terminology Criteria for Adverse Events (CTCAE), version 5) will be assessed |
Countries
Egypt
Contacts
Primary ContactAhmed M Mohamed, Master
Outcome results
None listed