Apparent Amoxapine Nephrotoxicity: Dependence on Rhabdomyolysis and Acidosis
The tricyclic antidepressant, amoxapine, has been released for distribution in the USA and in Europe. Acute renal failure has sometimes followed (Pumariega et al, 1982) attempts at suicide using this drug, but the incidence has been unpredictable and ranged from 10–15%, which suggests that other factors in addition to high doses of amoxapine and seizures may be involved. The available data in the literature shows that severe acidosis was frequently associated with amoxapine overdose. Goldberg and Spector (1982) described a patient whose blood pH dropped to 6.78 within 2 hr of ingesting nearly 60 mg/kg of amoxapine. Similarly, Rogol et al (1984) reported a blood pH of 6. 83 in an infant considered to be overdosed with amoxapine. Shepard (1983) reported a profound acidosis in a 15 month child that had accidentally ingested 25 mg/kg of the drug and developed a blood pH of 6. 91. In light of the frequent occurrence of acidosis following overdosage with amoxapine, the possibility exists that it may serve as a major contributing factor in the development of amoxapine-associated renal impairment. We therefore determined the effect of acidosis on the ability of high dosage amoxapine and seizures to produce apparent renal impairment in the rat. Because of the central role of muscle injury in atraumatic rhabdomyolytic acute renal failure in vivo, we also examined the potential of amoxapine to directly produce muscle injury in vitro.
KeywordsRenal Impairment Acute Renal Failure Muscle Injury Creatine Phosphokinase Nonionic Species
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