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dc.contributor.authorLind, Michael J
dc.contributor.authorMargison, Jennifer M
dc.contributor.authorCerny, T
dc.contributor.authorThatcher, Nick
dc.contributor.authorWilkinson, Peter M
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.
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
html.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.


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