A pilot pharmacokinetic study of tricyclic antidepressant ovine Fab for TCA poisoning in children

Nil Üfer Yalindag-Öztürk, Collin S. Goto, Greene Shepherd, Olivia Nayeli Torres, Brett Giroir

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Context.A pilot study of tricyclic antidepressant (TCA)-specific antibody fragments (TCA Fab) in TCA-intoxicated adults showed a marked increase in serum total TCA concentrations following TCA Fab infusion with no worsening signs of TCA toxicity. TCA Fab pharmacokinetics (PK) was not described in this adult study. The objective of this study was to evaluate the PK of TCA Fab in children with TCA poisoning.Methods.This was an open-label, single-center, dose escalation pilot trial of three patients. Inclusion criteria were documented TCA ingestion with at least one serious complication (QRS prolongation, dysrhythmia, hypotension, seizure, or coma). Patients were assigned to either a low-dose intravenous TCA Fab regimen (15, 30, and 60 mgkg) or a high-dose regimen (30, 60, and 120 mgkg) as needed to reverse TCA toxicity. Following the administration of TCA Fab, samples of blood and urine were obtained for PK evaluations. The outcomes of interest were serum and urine TCA concentrations (free and total), serum and urine Fab concentrations, improvement or worsening of TCA toxicity, and adverse effects.Results.Three study patients were 11, 11, and 14 years of age. Two patients received 15 mgkg of TCA Fab and one patient received a total of 90 mgkg of TCA Fab (30 60 mgkg). Serum-bound TCA increased significantly following TCA Fab administration with concomitant enhanced urinary elimination. Serum-free TCA concentrations were minimal to undetectable. Fab data were available for two patients. The serum TCA Fab area under the curve was 306.12 mgLh for the 15 mgkg dose and 2,198.10 mgLh for the 90 mgkg dose of TCA Fab. Maximum Fab concentrations correlated with maximum bound TCA in serum. The volume of distribution (VD) of TCA Fab was 0.20.3 Lkg. The clearance was 0.0360.05 Lkgh and the elimination half-life was 4 h. No adverse effects were observed.Conclusion.The limited PK data from this study are consistent with binding of TCA to TCA Fab and redistribution of TCA from the tissue to serum with subsequent enhanced urinary excretion of TCA. No toxic effects were observed with increased total TCA concentrations and no adverse effects were observed following TCA Fab administration. The small number of patients in this pilot study does not allow for safety or efficacy conclusions. copyright

Original languageEnglish (US)
Pages (from-to)418-423
Number of pages6
JournalClinical Toxicology
Volume48
Issue number5
DOIs
StatePublished - Jun 1 2010

Keywords

  • Drug-specific antibody
  • Fab pharmacokinetics
  • Toxicity
  • Tricyclic antidepressants

ASJC Scopus subject areas

  • Toxicology

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    Yalindag-Öztürk, N. Ü., Goto, C. S., Shepherd, G., Torres, O. N., & Giroir, B. (2010). A pilot pharmacokinetic study of tricyclic antidepressant ovine Fab for TCA poisoning in children. Clinical Toxicology, 48(5), 418-423. https://doi.org/10.3109/15563651003796358