Paradoxical relationship between acetylator phenotype and amonafide toxicity
Autor: | Linda Janisch, Mark J. Ratain, Rosemarie Mick, Richard L. Schilsky, Julie Smiddy, F Berezin, Stephanie F. Williams |
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Rok vydání: | 1991 |
Předmět: |
Male
Drug Metabolite medicine.medical_treatment media_common.quotation_subject Organophosphonates Antineoplastic Agents Pharmacology Biology Imides chemistry.chemical_compound Pharmacokinetics medicine Humans Pharmacology (medical) Prospective Studies media_common Chemotherapy Leukopenia Adenine Body Weight Acetylation Amonafide Middle Aged Isoquinolines Naphthalimides Phenotype chemistry Toxicity Female medicine.symptom Caffeine |
Zdroj: | Clinical Pharmacology & Therapeutics. 50:573-579 |
ISSN: | 1532-6535 0009-9236 |
Popis: | Patients receiving the investigational antineoplastic agent amonafide underwent prospective determination of acetylator phenotype with use of caffeine as a test drug. Fast acetylators of caffeine had significantly greater toxicity (myelosuppression) after amonafide treatment than slow acetylators, presumably because of greater conversion of amonafide to the active acetylated metabolite. Furthermore, the estimated area under the plasma concentration-time curve of amonafide was significantly greater in the fast acetylators, indicating that the total plasma clearance was paradoxically lower in this group. It is hypothesized that this paradox is attributable to competition for oxidation of amonafide by its acetylated metabolite (parallel pathway interaction). Pretreatment white blood count and patient age were also independent predictors of leukopenia. In addition, it was noted that the ratio of actual to ideal body weight was significantly higher in the fast acetylators. Studies are in progress to determine the optimal amonafide dose in both acetylator subgroups. |
Databáze: | OpenAIRE |
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