A sensitive method for the determination of plasma and urinary 4(5)-amino-5(4)-imidazole carboxamide

Skibba, Joseph L.; Beal, Diane D.; Bryan, George T.

doi:10.1016/0006-2944(69)90006-4

Biochemical Medicine

1969

DOI: 10.1016/0006-2944(69)90006-4

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A sensitive method for the determination of plasma and urinary 4(5)-amino-5(4)-imidazole carboxamide

Joseph L. Skibba

Diane D. Beal

George T. Bryan

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1970

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Cited by 10 publications

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“…Urinary AIC was determined by the method of Skibba et al [ 5 ] . The AIC standard was obtained from Sigma Chemical Company.…”

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confidence: 99%

4‐aminoimidazole‐5‐carboxamide excretion in acute leukemia

Johnson

Lapin

1978

Med. Pediatr. Oncol.

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The urinary excretion of 4-aminimidazole-5-carboxamide (AIC) as been reported to be increased in children with acute leukemia and has been correlated with disease status. Using a modification of the method of Skibba et al [5], determinations were made on urine from 26 children with acute leukemia. The urine from ten normal children served as controls. The effect of chemotherapy on urinary AIC was studied comparing patients on vincristine and prednisone (V+P) with those on 6-mercaptopurine, methotrexate, and cyclophosphamide (Triple Rx). Patients in remission on Triple Rx had lower levels of urinary AIC than did patients on Triple Rx in relapse or patients on V+P in either remission or relapse. Twenty patients had sequential measurements. Values for individual patients were not predictive of disease status. One such patient is described. This study demonstrates that chemotherapy, as well as disease status, affects the urinary excretion of AIC in children with acute leukemia.

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“…Urinary AIC was determined by the method of Skibba et al [ 5 ] . The AIC standard was obtained from Sigma Chemical Company.…”

mentioning

confidence: 99%

4‐aminoimidazole‐5‐carboxamide excretion in acute leukemia

Johnson

Lapin

1978

Med. Pediatr. Oncol.

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Colorimetric Method for Determination of Guanazole in Blood and Urine

Lower¹,

Bryan

Musa

1973

Journal of Pharmaceutical Sciences

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Pharmacokinetics of dacarbazine (DTIC) and its metabolite 5-aminoimidazole-4-carboxamide (AIC) following different dose schedules

Breithaupt

Dammann

Aigner³

1982

Cancer Chemother. Pharmacol.

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The pharmacokinetics of dacarbazine (DTIC) and its main metabolite 5-aminoimidazole-4-carboxamide (AIC) have been studied in eight patients with malignant melanoma or sarcoma receiving 2.65--6.85 mg DTIC/kg body weight by intravenous bolus injection or by continuous 0.5--6-h infusions on 5 consecutive days. The plasma disappearance of DTIC was biphasic, with a terminal half-life of 41.4 min (range 30.3--51.6 min). The mean distribution volume of DTIC was 0.632 liters/kg and the total clearance was 15.4 ml/kg . min (range 8.7--23.3 ml/kg . min). The renal clearance of DTIC was 5.2--10.9 ml/kg . min, indicating that about 50% of DTIC was eliminated by extrarenal mechanisms. The plasma decay of AIC was mono-exponential with a half-life of 43.0--116 min. A renal clearance of 2.6--5.3 ml/kg . min was calculated for AIC. The urinary recovery was 46%--52% for DTIC and 9%--18% for AIC. The plasma concentrations of DTIC observed during 0.5--6-h infusions of DTIC (5.45--6.85 mg/kg) were 0.66--6.2 micrograms/ml. Comparison of various dosage schedules within the same patient did not reveal relevant differences of the areas under the concentration-time curves. Immunotherapy with Bacillus Calmette-Guérin (BCG) did not significantly influence the pharmacokinetics of DTIC. During isolated extremity perfusion with DTIC (75--130 mg/kg extremity) for treatment of malignant tumors of the extremities concentrations of DTIC ranged from 150--500 micrograms/ml perfusate. There was no evidence of AIC formation. In isolated liver perfusion experiments in anesthetized dogs metabolic degradation of DTIC to AIC was demonstrated.

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A sensitive method for the determination of plasma and urinary 4(5)-amino-5(4)-imidazole carboxamide

Cited by 10 publications

References 17 publications

4‐aminoimidazole‐5‐carboxamide excretion in acute leukemia

4‐aminoimidazole‐5‐carboxamide excretion in acute leukemia

Colorimetric Method for Determination of Guanazole in Blood and Urine

Pharmacokinetics of dacarbazine (DTIC) and its metabolite 5-aminoimidazole-4-carboxamide (AIC) following different dose schedules

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