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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1983-2-14
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0344-5704
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
103-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7172404-Adult,
pubmed-meshheading:7172404-Aminoimidazole Carboxamide,
pubmed-meshheading:7172404-Dacarbazine,
pubmed-meshheading:7172404-Drug Administration Schedule,
pubmed-meshheading:7172404-Female,
pubmed-meshheading:7172404-Half-Life,
pubmed-meshheading:7172404-Humans,
pubmed-meshheading:7172404-Imidazoles,
pubmed-meshheading:7172404-Infusions, Parenteral,
pubmed-meshheading:7172404-Injections, Intravenous,
pubmed-meshheading:7172404-Kinetics,
pubmed-meshheading:7172404-Liver,
pubmed-meshheading:7172404-Male,
pubmed-meshheading:7172404-Middle Aged,
pubmed-meshheading:7172404-Time Factors
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pubmed:year |
1982
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pubmed:articleTitle |
Pharmacokinetics of dacarbazine (DTIC) and its metabolite 5-aminoimidazole-4-carboxamide (AIC) following different dose schedules.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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