ABSTRACT
Recent evidence of the emergence of resistance of P. vivax to chloroquine in Myanmar has increased the importance and urgency of understanding the cause of resistance as well as the need for devising the strategies to limit its spread. A comparative multiple-dose pharmacokinetic study was conducted on 5 clinically healthy volunteers and 10 malaria patients with P. vivax, admitted to the No. 2 Miliysty Hospital, Yangon, with the object to study whether there is any pharmacokinetic-dynamic relationship underlying the response of patients to standard chloroquine (1500 mg given over 3 days) therapy. Serum chloroquine concentrations reached well above the MIC level in all subjects with the patients' serum concentration (both peak and trough) and the AUC being significantly (2-3 times) higher than jnormal volunteers (p < 0.02). Both the clearance and the volume of distribution were also significantly lower in the malaria patients as compared to the healthy volunteers (p < 0.05). The elimination half-life (T1/2el) was shorter in malaria patients but the difference was not statistically significant. No significant difference was seen with other pharmacokinetic parameters, between normal volunteers and patients and between patients who do and do not recrudescenced. The study supports the emergence of chloroquine-resistant P. vivax in Myanmar and also excludes the possibility of apparent resistance due to pharmacokinetic causes, especially reduced bioavailability.