title: Pharmacological correlation between total drug concentration and lactones of CPT-11 and SN-38 in patients treated with CPT-11.
abstract: The pharmacokinetics of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were examined to establish the pharmacokinetic variability of the active lactones of CPT-11 and SN-38 in comparison with that of the total (lactone and carboxylates) plasma CPT-11 and SN-38. Twelve patients with malignancies were entered in the study. All received 100 mg/m2 of CPT-11 by intravenous drip infusion over 90 min. Blood was sampled at 10 time points in heparin-containing syringes. Analysis by high-performance liquid chromatography showed that the ratio of CPT-11 lactone to total CPT-11 concentration was highest (66%) just after the end of infusion and gradually decreased to 30% at 24 h. Almost 70% of SN-38 lactone was detected after the end of infusion and this decreased to 50% within 24 h. The standard errors of percent lactone of CPT-11 of SN-38 to total drug concentration at each sampling point were less than 12%. The area under the concentration-time curve (AUC) of total CPT-11 and that of total SN-38 were significantly correlated with the AUCs of the lactone CPT-11 and those of lactone SN-38, respectively. We conclude that, for practical purposes, monitoring of total CPT-11 and SN-38 has essentially the same clinical significance as monitoring of lactone CPT-11 and SN-38.
authors.affiliation: Department of Medicine, National Cancer Center Hospital East, Chiba.
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Sudoh
authors.forename: H
authors.initials: H
authors.lastname: Hakusui
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Ohtsu
authors.forename: H
authors.initials: H
authors.lastname: Wakita
authors.forename: T
authors.initials: T
authors.lastname: Igarashi
authors.forename: K
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007700:Kinetics; D007783:Lactones / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood*; D011446:Prospective Studies
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D000077146:Irinotecan; D002166:Camptothecin