We read with great interest the study by Brahmi et al [1x[1]Brahmi, N., Kouraichi, N., Thabet, H. et al. Influence of activated charcoal on the pharmacokinetics and the clinical features of carbamazepine poisoning. Am J Emerg Med. 2006; 24: 440–443

Abstract | Full Text | Full Text PDF | PubMed | Scopus (19)See all References][1] examining the effect of multiple-dose activated charcoal (MDAC) in carbamazepine (CBZ) poisoning. We applaud their prospective design, but we have questions about their group selection and half-life calculations.

Both groups received 1 dose of activated charcoal at t = 0 hours; no additional intervention differentiated the 2 groups until t = 6 hours. Despite similar treatment over that initial 6-hour period, figure 1 demonstrates dramatically divergent courses in the 2 groups before the study intervention (MDAC) at 6 hours is even initiated: CBZ concentrations continue to rise in the non-MDAC group. Does this suggest that the non-MDAC group ingested higher quantities of CBZ, or that their ingestion time was more recent, thereby representing fundamental differences between the groups?

Most readers will recall the term “half-life” (t_1/2) as ideally applicable to processes obeying first-order kinetics. As such, plasma concentration at any given time (t) can be described as C_t = C₀e^−kt. In this study, solving for t_1/2 involves curve fitting a logarithmic equation to 2 given points. It has been documented, however, that elimination of CBZ in overdose follows zero-order kinetics [[2]x[2]Winnicka, R., Lopacinski, B., Szymczak, W. et al. Carbamazepine poisoning: elimination kinetics and quantitative relationship with the carbamazepine 10,11-epoxide. J Toxicol Clin Toxicol. 2002; 40: 759–765

CrossRef | PubMed | Scopus (16)See all References, [3]x[3]Perez, A. and Wiley, J.F. Pediatric carbamazepine suspension overdose—clinical manifestations and toxicokinetics. Pediatr Emerg Care. 2005; 21: 252–254

CrossRef | PubMed | Scopus (66)See all References]. Cumulative kinetics in the plasma are more complicated as redistribution from tissues and residual gastrointestinal absorption are additive with hepatic metabolism [4x[4]Levy, R.H., Pitlick, W.H., Troupin, A.S. et al. Pharmacokinetics of carbamazepine in normal man. Clin Pharmacol Ther. 1975; 17: 657–668

PubMedSee all References][4], although plasma concentration clearly degrades in a linear rather than logarithmic fashion. Half-life, then, is not a constant value; it varies with substance concentration. In comparing in vivo half-lives of CBZ after a single activated charcoal dose against half-lives calculated after MDAC (at much lower concentrations), the resulting difference should likely be expected and does not necessarily imply successful intervention.

Prospective studies in poisoned patients are challenging to carry out. Although we question the strength of their conclusions, we look forward to further studies investigating MDAC in CBZ poisoning.