Comparative study of interactions between chloroquine and chlorpheniramine or promethazine in healthy volunteers: a potential combination-therapy phenomenon for resuscitating chloroquine for malaria treatment in Africa.

Although, in in-vitro and limited in-vivo studies, chlorpheniramine (CP) and promethazine (PR) have each been shown to reverse chloroquine (CQ) resistance, the pharmacokinetic basis of this reversal has not been fully elucidated. In the present study, 15 healthy volunteers were randomly allotted to receive standard doses of CQ alone or in combination with CP or PR. Blood samples were collected from each volunteer at 21 time-points, from immediately before to 168 h after the initial dose. These samples were used to follow the changes in the plasma and erythrocytic concentrations of CQ. The ratio between the mean maximum CQ concentration in the erythrocytes and that in the plasma was 4.2 for the volunteers given CQ alone, 7.3 in those given CQ-CP, and 3.2 in those given CQ-PR. CP significantly enhanced the erythrocytic accumulation of CQ, increasing the maximum CQ concentration observed in the erythrocytes by 24% (P = 0.02). The bio-availability of CQ was also significantly increased in the presence of CP, with the mean value for the area under the curve, of erythrocytic concentration v. time, increasing from 99,921 to 214,516 ng/ml.h (P=0.001). The mean half-life of CQ in the erythrocytes also increased when CP was used, from 51 to 100 h, but this change was not statistically significant (P=0.83). In contrast to CP, PR had no statistically significant effect on the disposition of CQ. As CP clearly enhances disposition of CQ, a combination of CQ with CP may be useful in the management of CQ-resistant infections. Detailed toxicological studies are required to understand the full clinical implications of CP's elevation of erythrocytic CQ concentrations.

Plasmodium berghei: efficacy and safety of combinations of chloroquine and promethazine in chloroquine resistant infections in gravid mice.

Efficacy and safety of combinations ofChloroquine (CQ) and doses of Promethazine (PR) against CQ resistant Plasmodium berghei infections in gravid mice was evaluated. Parasites were cleared faster in mice treated with CQ combined with doses of PR ranging from 20mg/kg to 50mg/kg (3.4 +/- 0.5 to 2.7 +/- 0.7) compared with CQ alone (4.7 +/- 0.8) (P<0.5). Parturition resulting in live pups in animals treated with CQ and 20mg/ kg and 30mg/kg of PR (81%) was significantly higher than in animals treated with CQ alone (44%) or saline (13%). Mean birth weight of pups delivered by infected gravid animals treated with CQ and 30mg/kg or 40mg/kg of PR (1.51 +/- 0.16 or 1.56 +/- 0.16) was significantly higher than animals treated with CQ alone (1.33 +/- 0.13) (P=0.00004, 0.0014 respectively). No gross malformations were observed in pups delivered by infected or non-infected animals treated with the combinations of chloroquine and Promethazine.

Cultural categorization of febrile illnesses in correlation with herbal remedies used for treatment in Southwestern Nigeria.

The ethnographic study was conducted in two communities in Oyo State in Southwestern Nigeria. The study sites consisted of a rural and an urban local government area located in the tropical rain forest zone of Nigeria. The study was designed to obtain information on febrile illnesses and herbal remedies for treatment with the aim of identifying potential antimalarial drugs. The study revealed that fever is a general term for describing illnesses associated with elevated body temperature. The indigenous Yoruba ethnic population has categorized fever based on symptoms and causes. The present communication is the result of focus group discussion and semi-structured questionnaire administered to traditional healers, herb sellers, elders and mothers. This was on types of fevers, symptoms and causes of febrile illnesses. The investigation also included use of traditional herbs in the prevention and treatment of the illnesses in the two communities.A total of 514 respondents were interviewed. This was made up of 266 (51.8%) from Atiba local government area (LGA), an urban centre while 248 (48.2%) respondents were interviewed from Itesiwaju LGA, a rural community. The LGAs are located in Oyo State of Nigeria. The respondents proffered 12 types of febrile illnesses in a multiple response answering system in Yoruba language. The most common ones (direct translation into English) were: yellow fever (39.1%), typhoid (34.8%), ordinary (28.8%), rainy season (20.8%) and headache (10.5%) fevers, respectively. Perceived causes of each of the febrile illnesses included stress, mosquito bites, unclean water, rains and over exposure to the sun. Methods of fever prevention were mainly with the use of herbal decoctions, powdered herbs, orthodox medications and maintenance of proper hygiene. Of a total of 112 different herbal remedies used in the treatment of the febrile illnesses compiled from the study, 25 recipes are presented. Recipes consisted of 2-7 ingredients. Oral decoctions (84%), oral powders (63%), use as soaps and creams (40%) in a multiple response system, were the most prevalent routes of administration of prepared herbs used in the treatment of the fevers. Boiling in water or alcohol was the most common method used in the preparation of the remedies. The four most frequently mentioned (multiple response system) plants in the Southwest ethnobotany for fevers were Azadirachta indica (87.5%), Mangifera indica (75.0%), Morinda lucida (68.8%) and Citrus medica (68.8%).