title: Effects of gender, age, and race on the pharmacokinetics of etoposide after intravenous administration of etoposide phosphate in cancer patients.
abstract: The influence of gender, age, and race on the pharmacokinetics of etoposide and on the extent of conversion of etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) to etoposide are summarized. Included in the integrated statistical analyses were 192 patients from six phase I/II studies (102 men and 90 women, 128 aged < or = 65 years and 64 aged > 65 years; 134 were white, 18 were other races, and race was not recorded for 40). The dose of etoposide phosphate ranged from 25 to 200 mg/m2 of etoposide equivalents and was administered as 5-(bolus) to 210-minute intravenous infusions. Total body clearance of etoposide was comparable between men and women. However, significantly lower steady-state volumes of distribution and shorter half-lives were observed in women relative to men. Patients who were older than 65 years had significantly lower etoposide total body clearance and longer half-lives than younger patients. The gender- and age-related differences observed in the pharmacokinetic parameters of etoposide were significant but generally of a small magnitude (< or = 13%), indicating no need for dose adjustment in these patient populations. There were no significant race-related differences in the pharmacokinetic parameters of etoposide. All patients showed rapid conversion of etoposide phosphate to etoposide. The individual area under the plasma concentration-time curve ratio of etoposide phosphate/etoposide was < or = 0.0324, indicating that etoposide was the major circulating moiety after infusion of etoposide phosphate. Significant gender-, age-, or race-related differences in the area under the plasma concentration-time curve ratios were not observed. An evaluation of the area under the plasma concentration-time curve ratios with respect to infusion time suggested that the conversion of etoposide phosphate to etoposide was independent of infusion time.
authors.affiliation: Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kaul
authors.forename: N R
authors.initials: NR
authors.lastname: Srinivas
authors.forename: V
authors.initials: V
authors.lastname: Mummaneni
authors.forename: L N
authors.initials: LN
authors.lastname: Igwemezie
authors.forename: R H
authors.initials: RH
authors.lastname: Barbhaiya
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003627:Data Interpretation, Statistical; D005047:Etoposide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044469:Racial Groups; D012737:Sex Factors
chemical_list: D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; C061400:etoposide phosphate; D005047:Etoposide