Bioavailability at oral chloroquine in Children with uncomplicated malaria and acute watery diarrhoea co-morbidity

Until recently chloroquine (CQ) has been the first line drug treatment of uncomplicated malaria in Tanzania. However the current overall treatment failure is 52%. Possible reasons for this high rate could be due to parasite resistance, poor quality of the drug, poor compliance, inadequate dose or poor drug absorption when give orally as it may occur in patients with diarrhoea. In order to asses; the effect of diarrhoea on absorption of oral CQ, bioavailability was determined in 20 children with both uncomplicated malaria and Acute Watery Diarrhoea (group I) and compared with 18 children having uncomplicated malaria without diarrhoea, (group II). Children were treated with oral CQ tablets, 10 mg Chloroquine base/kg body weight on two consecutive days and 5mg/kg on the third day. 75µ1. of blood from finger prick were collected in heparinised capillary tubes immediately before first dose of chloroquine and then at 1, 4, 8, 24, 48, 168, and 336 hours. The blood was then transferred on filter paper strips that were air dried and stored separately in sealed plastic envelopes at room temperature until analyzed for CQ and desethylchloroquine (DECQ) concentrations. Results revealed that although the concentrations of CQ and DECQ were higher in group II children than those in group I from t1 onwards the difference was only statistically significant at t4 (p = 0.0003), t8(p = 0.0002) and t 24. (p = 0.005). Maximum plasma concentration (Cpmax) of CQ was also significantly higher in group II children with mean of 2209 ± 694.8nmol/L compared to 1531 ± 695.1nmo1/L in group I children, (p value 0.005). Furthermore, Cpmax for DECQ was also higher in group II children, mean 930.4± 455.2 nmol/ L compared to a mean of 555.6 ± 283.7 nmo1/L in children in group I, (p-value 0.014). The area under the plasma concentration time curve (AUC) for CQ and DECQ calculated from 0 - 24, 24 - 48, 48 - 168 and 168 - 336 hours showed significantly higher levels in group II than in group I children. Bioavailability of CQ and DECQ was not affected by mild to moderate malnutrition and some dehydration. Likewise duration and frequency of diarrhoea before CQ intake had no effect on the value of AUC. However, frequency of diarrhoea after CQ intake was inversely related to AUC measured from 0 to 24 hours. These results show evidence of poor absorption of CQ in children with diarrhoea. It is recommended that children with both uncomplicated malaria and diarrhoea should receive parenteral chloroquine in favour of the oral route.