Clinical pharmacology of isophosphamide

Creaven, Patrick J.; Allen, Larry M.; Alford, Dorothy A.; Cohen, Martin H.

doi:10.1002/cpt1974161part177

Cited by 52 publications

(26 citation statements)

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“…Creaven et al (1974) reported the persistence of plasma NBP alkylating activity in four ifosfamide treated patients for up to 24 h and for 48 h in two others. Brock et al…”

Section: Discussionmentioning

confidence: 98%

The pharmacokinetics of ifosfamide given as short and long intravenous infusions in cancer patients.

Lewis

Fitzgerald

Mohan

et al. 1991

Brit J Clinical Pharma

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1 We investigated the pharmacokinetics of ifosfamide 5 g m-2 given by two regimens.Six patients (one female), median age 55 (range 40-71) years, all with lung cancer received 5 g m-2 ifosfamide (median ifosfamide dose 8.95 g) as an intravenous infusion over 0.5 h with mesna. Four other cancer patients (all male) of median age 52.5 (range 23-72) years were studied on seven treatment occasions with 5 g m-2 ifosfamide (median ifosfamide dose 8.88 g) as a 24 h intravenous infusion with mesna. Plasma was assayed for ifosfamide by gas liquid chromatography and for alkylating activity by the nitrobenzylpyridine method. 2 After ifosfamide 5 g m-2 infused over 0.5 h, the decay of the plasma ifosfamide concentration was monoexponential with a median (range) t/2,z of 5.4 h (3.6-10.4 h).The median clearance was 60 ml min-1 (47-104) and the median volume of distribution was 388 (329-783) ml kg-'. Plasma nitrobenzylpyridine alkylating activity showed a biexponential decay in four patients and a monoexponential decay in two, with a median AUC of 102 (24-177) nmol nor nitrogen mustard eq h ml-'.3 When ifosfamide 5 g m-2 was given as a 24 h infusion, the decay of the plasma ifosfamide concentration was monoexponential, the median (range) t/2,z was 4.5 (3.4-6.1), the median volume of distribution was 563 (292-818) ml kg-1 and the median clearance was 79 (59-116) ml min-1. Plasma nitrobenzylpyridine alkylating activity decayed monoexponentially and the median AUC was 49 (45-131) nmol nor nitrogen mustard eq ml-' h.4 There was no evidence of saturation kinetics after high doses of ifosfamide. The clearance of ifosfamide at 5 g m-2 was similar whether it was given by short or 24 h intravenous infusion and was comparable with that observed after low doses of ifosfamide.

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“…Creaven et al (1974) reported the persistence of plasma NBP alkylating activity in four ifosfamide treated patients for up to 24 h and for 48 h in two others. Brock et al…”

Section: Discussionmentioning

confidence: 98%

The pharmacokinetics of ifosfamide given as short and long intravenous infusions in cancer patients.

Lewis

Fitzgerald

Mohan

et al. 1991

Brit J Clinical Pharma

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“…The median interval between the last day of mobilization chemotherapy and the first apheresis was 10 days (8)(9)(10)(11)(12)(13)(14) for the IFO+GM-CSF group and 13 days (8-25) for the CY+GM-CSF group (P = 0.002). GM-CSF was administered for a median of 9 days (7-13) and 15 days (9-31), respectively (P = 0.001).…”

Section: Leukapheresis Mononuclear Cell and Cd-34 + Yieldmentioning

confidence: 99%

“…Approximately 3.5 g/m 2 of ifosfamide has equivalent antineoplastic activity to 1 g/m 2 of cyclophosphamide. 13 This drug has been used in PBPC mobilization in combination with other chemotherapy drugs 14,15 but has not been described as a single agent.…”

mentioning

confidence: 99%

Prospective randomized clinical trial comparing high-dose ifosfamide + GM-CSF vs high-dose cyclophosphamide + GM-CSF for blood progenitor cell mobilization

Vela‐Ojeda

Tripp-Villanueva

Montiel‐Cervantes

et al. 2000

Bone Marrow Transplant

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Summary:Between August 1994 and June 1999, 56 patients were prospectively randomized to receive ifosfamide 10 g/m 2 + GM-CSF 5 g/kg/day (IFO+GM-CSF n = 28) and cyclophosphamide 4 g/m 2 + GM-CSF 5 g/kg/day (CY+GM-CSF n = 28). Both groups were comparable for age, gender, diagnosis, disease stage and previous chemotherapy. The IFO+GM-CSF group demonstrated a shorter median interval between therapy and apheresis (10 days (8-14) vs 13 days (8-25) P = 0.002), median number of doses of GM-CSF (9 (7-13) vs 15 (9-31) P = 0.001), median of days with aplasia (0.5 (0-10) vs 6 (0-21) P = 0.001), median days with fever (0 (0-6) vs 3 (0-9) P = 0.006) and median of days using i.v. antibiotics (0 (0-11) vs 7.5 (0-19) P = 0.002). The median MNC yield was similar in both groups. The CD34 + cell yield was better in the CY+GM-CSF group (3.14 (0.9-11.8) vs 5.33 (0.08-32)) but not at significant levels (P = 0.1). White blood cell hematopoietic recovery was more rapid in the CY+GM-CSF group (16 (10-22) vs 13 (10-24) P = 0.02). Platelet engraftment was similar in both groups. Costs of mobilization and transplantation were almost the same: $28 570 ($18 527-$47 028) and $30 020 ($17 281-$67 591), respectively (P = 0.9). There were no differences in disease-free survival and overall survival between both groups. Mild and transient non-hematological toxicity (hemorrhagic cystitis, decrease in serum creatinine clearance and CNS dysfunction) was seen most frequently in the IFO+GM-CSF group. Bone Marrow Transplantation (2000) 25, 1141-1146.

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“…IFOS is a prodrug, requiring biotransformation for activity or toxicity (Allen and Creaven, 1972;Creaven et al, 1974). Metabolism appears to be mainly in the liver where cytochrome P450 enzymes produce the active intermediate 4 OH ifosfamide (Brock and Hohorst, 1963).…”

mentioning

confidence: 99%

The pharmacokinetics and metabolism of ifosfamide during bolus and infusional administration: a randomized cross-over study

Singer

Hartley²,

Brennan³

et al. 1998

Br J Cancer

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Summary In a randomized cross-over trial, 11 patients received ifosfamide (IFOS) in 21-day cycles, which alternated between 3 g m-2 x (2 or 3) days given as a 1-h bolus doses, or the same total dose as a continuous infusion. Patients who received four or more cycles also alternated between two cycles on dexamethasone 4 mg 8 hourly for 3 days starting 8 h before IFOS, and two cycles off dexamethasone. A total of 34 patient cycles were studied and serum and urinary levels of IFOS, 2 dechloroethylifosfamide (2DC), 3 dechloroethylifosfamide (3DC), carboxyifosfamide (CX) and isophosphoramide mustard (IPM) were measured by thin-layer chromatography. No significant differences could be detected in the areas under the curve (AUCs) of serum concentration, nor in the proportion of IFOS or its metabolites found in the urine. There was no significant effect of dexamethasone on IFOS metabolism. These results indicate that there is no identifiable pharmacokinetic basis for insistence on either bolus or infusional methods of IFOS administration.

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Clinical pharmacology of isophosphamide

Cited by 52 publications

References 0 publications

The pharmacokinetics of ifosfamide given as short and long intravenous infusions in cancer patients.

The pharmacokinetics of ifosfamide given as short and long intravenous infusions in cancer patients.

Prospective randomized clinical trial comparing high-dose ifosfamide + GM-CSF vs high-dose cyclophosphamide + GM-CSF for blood progenitor cell mobilization

The pharmacokinetics and metabolism of ifosfamide during bolus and infusional administration: a randomized cross-over study

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