Inter- and intrapatient variability in etoposide kinetics with oral and intravenous drug administration.
نویسندگان
چکیده
The objective of this study was to accurately determine the within- and between-patient variability in etoposide pharmacokinetics for i.v. and p.o. administered drug. Inter-and intrapatient variability in systemic etoposide exposure was measured following i.v. and p.o. drug administration using stable isotope dilution methodology. Seven patients received 50 mg of etoposide by both p.o. and i.v. routes of administration on three separate occasions 1 month apart. Etoposide plasma concentrations following p.o. and i.v. drug administration were quantitated by liquid chromatography-mass spectrometry for each route of administration. The area under the plasma etoposide concentration versus time curve, plasma etoposide clearance, and etoposide plasma half-life were calculated for each dose of drug. Kinetic measurements following i.v. and p.o. drug administration were compared. The within-patient variation in the areas under the plasma etoposide concentration versus time curves following i.v. drug administration was minimal [coefficient of variation (CV) = 9.3%]. Within-patient variability was increased 2.4-fold with oral drug administration (intrapatient CV = 22.2%). Between-patient variability was roughly three times as great as within-patient variability (interpatient i.v. CV = 28.4%; interpatient p.o. CV = 58.3%). Mean etoposide bioavailability at a dose of 50 mg was 64.6%, again with greater interpatient than intrapatient variability (34.8 versus 22.6%). Greater variation in drug toxicity is expected with p.o. compared with i.v. etoposide use. Administration of repeated doses of etoposide to the same patient should produce less variation in toxicity than between-patient dosing.
منابع مشابه
Oral cancer chemotherapy: the promise and the pitfalls.
The future for oral cancer chemotherapy has never been brighter. The need to move cancer treatment from a predominantly hospital-based, inpatient system into the ambulatory setting has joined with the growing body of information demonstrating higher antitumor activity, lower systemic toxicity, or both with dosing regimens that produce prolonged exposure to some cancer chemotherapy. This has led...
متن کاملOral treatment with etoposide in small cell lung cancer – dilemmas and solutions
BACKGROUND Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavaila...
متن کاملپایش درمانی سیکلوسپورین-آ در کودکان ایرانی با کلیه پیوندی
Background & Aim: Cyclosporine-A (CsA) is an immunosuppressant with a narrow therapeutic window. Inter-and-intrapatient variability in cyclosporine pharmacokinetics necessitates frequent blood level monitoring in transplant patients and total blood cyclosporine concentration used to allow dosage adjustment in transplant patients. The purpose of the present study was, first of all, to develop ...
متن کاملPlasma pharmacokinetics of pioglitazone following oral or intravenous administration in Holstein cows
Pioglitazone belongs to the thiazolidinedione (TZD) class of antidiabetic agents, with proven efficacy in increasing insulin sensitivity and in the treatment of type 2 diabetes mellitus in humans. Pioglitazone has been proposed as a potential feed additive to reduce insulin resistance and consequently some of the metabolic disorders in transition cows. This study was aimed at determining the ph...
متن کاملLaboratory Monitoring of Cyclosporine Pre-dose Concentration (C0) After Kidney Transplantation in Isfahan
Background: Cyclosporine is the main immunosuppressive agent used in organ transplantation which leads to considerable improvement in graft survival. The large inter- and intra- patient variability in cyclosporine pharmacokinetics coupled with the agent’s narrow therapeutic index and adverse effects necessitate therapeutic monitoring of cyclosporine blood levels. Objective: The aim of this stu...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Clinical cancer research : an official journal of the American Association for Cancer Research
دوره 5 10 شماره
صفحات -
تاریخ انتشار 1999