Comparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/108098
Title:
Comparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma.
Authors:
Lind, Michael J; Margison, Jennifer M; Cerny, T; Thatcher, Nick; Wilkinson, Peter M
Abstract:
20 patients with advanced non-small cell lung cancer were treated with ifosfamide and mesna 1.5 g/m2 daily for 5 days; 10 received the drug by mouth and 10 i.v. Both schedules resulted in a reduction in the elimination half-life with an increased total and nonrenal clearance of ifosfamide over the 5-day period. Oral administration resulted in an unacceptably high incidence of encephalopathy(5/10) which was not seen in the i.v. group. In two patients this encephalopathy manifested itself as coma which lasted for 24 to 48 h but was fully reversible and in the other three cases as somnolence occurring for more than 50% of the patients' waking hours. Nadir blood counts and response rates were similar in both arms. The encephalopathy suggests that there are metabolic differences between the i.v. and oral routes and that a metabolite rather than the parent drug is responsible for this syndrome. In addition it was shown that the total and nonrenal clearance of the drug was significantly less when the drug was administered orally. None of the pharmacokinetic parameters either singly or in combination predicted for ifosfamide toxicity. No correlation between the creatinine clearance and ifosfamide renal clearance was demonstrated suggesting tubular reabsorption of the drug. In conclusion, ifosfamide cannot be given orally at the conventionally employed i.v. doses.
Affiliation:
CRC Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester, United Kingdom.
Citation:
Comparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma. 1989, 49 (3):753-7 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Feb-1989
URI:
http://hdl.handle.net/10541/108098
PubMed ID:
2910494
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLind, Michael Jen
dc.contributor.authorMargison, Jennifer Men
dc.contributor.authorCerny, Ten
dc.contributor.authorThatcher, Nicken
dc.contributor.authorWilkinson, Peter Men
dc.date.accessioned2010-07-21T15:09:42Z-
dc.date.available2010-07-21T15:09:42Z-
dc.date.issued1989-02-01-
dc.identifier.citationComparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma. 1989, 49 (3):753-7 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid2910494-
dc.identifier.urihttp://hdl.handle.net/10541/108098-
dc.description.abstract20 patients with advanced non-small cell lung cancer were treated with ifosfamide and mesna 1.5 g/m2 daily for 5 days; 10 received the drug by mouth and 10 i.v. Both schedules resulted in a reduction in the elimination half-life with an increased total and nonrenal clearance of ifosfamide over the 5-day period. Oral administration resulted in an unacceptably high incidence of encephalopathy(5/10) which was not seen in the i.v. group. In two patients this encephalopathy manifested itself as coma which lasted for 24 to 48 h but was fully reversible and in the other three cases as somnolence occurring for more than 50% of the patients' waking hours. Nadir blood counts and response rates were similar in both arms. The encephalopathy suggests that there are metabolic differences between the i.v. and oral routes and that a metabolite rather than the parent drug is responsible for this syndrome. In addition it was shown that the total and nonrenal clearance of the drug was significantly less when the drug was administered orally. None of the pharmacokinetic parameters either singly or in combination predicted for ifosfamide toxicity. No correlation between the creatinine clearance and ifosfamide renal clearance was demonstrated suggesting tubular reabsorption of the drug. In conclusion, ifosfamide cannot be given orally at the conventionally employed i.v. doses.en
dc.language.isoenen
dc.subject.meshAdministration, Oral-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAlkylation-
dc.subject.meshCarcinoma, Bronchogenic-
dc.subject.meshHumans-
dc.subject.meshIfosfamide-
dc.subject.meshInjections, Intravenous-
dc.subject.meshMiddle Aged-
dc.titleComparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester, United Kingdom.en
dc.identifier.journalCancer Researchen

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