Variable bioavailability following repeated oral doses of etoposide

Clinical pharmacological profile of etoposide in elderly patients with lung cancer

“…The main disadvantage of oral etoposide is the considerable variability in its bioavailability, with mean values ranging from 38 to 76% of the administered dose. 5,12,13 Joel et al reported that gastric motility and pH did not correlate with bioavailability of etoposide. 14 Etoposide undergoes first-pass elimination, which is mainly mediated by cytochrome P450 3A4 (CYP3A4) and P-glycoprotein.…”

Clinical pharmacological profile of etoposide in elderly patients with lung cancer

“…The main disadvantage of oral etoposide is the considerable variability in its bioavailability, with mean values ranging from 38 to 76% of the administered dose. 5,12,13 Joel et al reported that gastric motility and pH did not correlate with bioavailability of etoposide. 14 Etoposide undergoes first-pass elimination, which is mainly mediated by cytochrome P450 3A4 (CYP3A4) and P-glycoprotein.…”

Oral Etoposide (VP16) in Platinum-Resistant Epithelial Ovarian Cancer (EOC)

“…18 The oral bioavailability of etoposide shows marked inter-and intrapatient variability. 19 Once absorbed, it is largely bound to plasma proteins, with free drug being cleared by both renal and hepatic routes. There is therefore much potential net variability in the pharmacokinetics of the drug in patients with cancer, who may have altered gastrointestinal function, hypoproteinemia, and hepatic or renal dysfunction.…”

A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer

“…The activity reported with these oral regimens suggests that peak concentrations clearly contribute to activity, but the consequence of plasma concentration falling below an active range is not yet clear, and maintaining concentration within the active range throughout the treatment period, with infusional or hyper-fractionated oral dosing, may be more effective. Secondly the bioavailability of oral etoposide is incomplete and variable [9,33], both within and between patients, such that toxicity is largely unpredictable. Many of the studies with 10-21-day schedules of low daily dose etoposide report grade 3 or 4 leucopenia or neutropenia in a significant proportion of patients, while in patients with low bioavailability activity is likely to be low.…”

Clinical pharmacological profile of etoposide in elderly patients with lung cancer

“…The main disadvantage of oral etoposide is the considerable variability in its bioavailability, with mean values ranging from 38 to 76% of the administered dose. 5,12,13 Joel et al reported that gastric motility and pH did not correlate with bioavailability of etoposide. 14 Etoposide undergoes first-pass elimination, which is mainly mediated by cytochrome P450 3A4 (CYP3A4) and P-glycoprotein.…”

Oral Etoposide (VP16) in Platinum-Resistant Epithelial Ovarian Cancer (EOC)

“…18 The oral bioavailability of etoposide shows marked inter-and intrapatient variability. 19 Once absorbed, it is largely bound to plasma proteins, with free drug being cleared by both renal and hepatic routes. There is therefore much potential net variability in the pharmacokinetics of the drug in patients with cancer, who may have altered gastrointestinal function, hypoproteinemia, and hepatic or renal dysfunction.…”

A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer

“…The activity reported with these oral regimens suggests that peak concentrations clearly contribute to activity, but the consequence of plasma concentration falling below an active range is not yet clear, and maintaining concentration within the active range throughout the treatment period, with infusional or hyper-fractionated oral dosing, may be more effective. Secondly the bioavailability of oral etoposide is incomplete and variable [9,33], both within and between patients, such that toxicity is largely unpredictable. Many of the studies with 10-21-day schedules of low daily dose etoposide report grade 3 or 4 leucopenia or neutropenia in a significant proportion of patients, while in patients with low bioavailability activity is likely to be low.…”

Clinical pharmacological profile of etoposide in elderly patients with lung cancer

“…The main disadvantage of oral etoposide is the considerable variability in its bioavailability, with mean values ranging from 38 to 76% of the administered dose. 5,12,13 Joel et al reported that gastric motility and pH did not correlate with bioavailability of etoposide. 14 Etoposide undergoes first-pass elimination, which is mainly mediated by cytochrome P450 3A4 (CYP3A4) and P-glycoprotein.…”

Oral Etoposide (VP16) in Platinum-Resistant Epithelial Ovarian Cancer (EOC)

“…18 The oral bioavailability of etoposide shows marked inter-and intrapatient variability. 19 Once absorbed, it is largely bound to plasma proteins, with free drug being cleared by both renal and hepatic routes. There is therefore much potential net variability in the pharmacokinetics of the drug in patients with cancer, who may have altered gastrointestinal function, hypoproteinemia, and hepatic or renal dysfunction.…”

A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer

“…The activity reported with these oral regimens suggests that peak concentrations clearly contribute to activity, but the consequence of plasma concentration falling below an active range is not yet clear, and maintaining concentration within the active range throughout the treatment period, with infusional or hyper-fractionated oral dosing, may be more effective. Secondly the bioavailability of oral etoposide is incomplete and variable [9,33], both within and between patients, such that toxicity is largely unpredictable. Many of the studies with 10-21-day schedules of low daily dose etoposide report grade 3 or 4 leucopenia or neutropenia in a significant proportion of patients, while in patients with low bioavailability activity is likely to be low.…”