Dosage for malaria treatment

Abstract

We agree with Kain and colleagues that the use of salt and base prescriptions for antimalarial drugs is confusing. Dose recommendations for quinidine in severe malaria are based on two studies. In the first, intravenous quinidine gluconate, 15 mg base/kg over 4 h followed by 7·5 mg base/kg 8 hourly (ie, 52·5 mg/kg in 48 h), was given to 14 adult Thai patients with severe falciparum malaria. 2 Phillips RE Warrell DA White NJ et al. Intravenous quinidine for the treatment of severe falciparum malaria: clinical and pharmacokinetic studies. N Engl J Med. 1985; 312: 1273-1278 Crossref PubMed Scopus (96) Google Scholar Mean (range) total plasma quinidine concentrations were 9·2 (4·4–14·3) mg/L at the end of the initial loading dose infusion and then declined. A similar pattern over a nearly two-fold higher plasma concentration range has been noted previously for the treatment of severe malaria with quinine, the L-diastereoisomer of quinidine. 3 White NJ Looareesuwan S Warrell DA et al. Quinine loading dose in cerebral malaria. Am J Trop Med Hyg. 1983; 32: 1-5 PubMed Google Scholar In the second study intravenous quinidine, 6·2 mg base/kg infused over 1·2 h followed by 0·75 mg base/kg per h, a dose 22·5% lower than in the Thai study, was given in the USA. 4 Miller KD Greenberg AE Campbell CC Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange transfusion. N Engl J Med. 1989; 321: 65-70 Crossref PubMed Scopus (151) Google Scholar Five patients received quinidine alone, 12 also underwent exchange blood transfusion, which would have resulted in an increased free fraction of quinidine, changing the relation between total plasma quinidine, efficacy, and toxicity. Only two patients had plasma quinidine concentrations exceeding 7 mg/L, whereas in the Thai study all patients' plasma concentrations exceeded 5·8 mg/L after the initial infusion-a concentration thought to correspond with the maximum minimum inhibitory concentration for Thai Plasmodium falciparum isolates at the time.