Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered.

OBJECTIVE: To determine the effect of artesunate (AT) on the disposition kinetics of sulfadoxine/pyrimethamine (SP) in humans. METHODS: In a randomized cross-over study, 16 healthy volunteers were given a dose of three SP tablets containing 500 mg of sulfadoxine (SDX) and 25 mg of pyrimethamine (PYR) (=SP group), while the second arm received three SP tablets + two AT tablets of 200 mg in total followed by 100 mg AT for the next 4 days (SP+AT group). Blood samples (100 microl) were collected by means of a finger prick and dried on filter paper. The blood spots were wrapped in polythene folders and stored at room temperature until analysis. The samples were assayed using high-performance liquid chromatographic methods. RESULTS: The peak concentration C(max)), time required to attain peak concentration (T(max)), half-life (t ((1/2))) and area under the plasma concentration-time curve (AUC) were determined. The C(max) of SDX were 92.9 and 98.9 microg/ml for the SP and SP+AT arms, respectively; for PYR, these were 0.86 and 0.79 microg/ml, respectively. The T(max) of SDX were 10 and 8 h for the SP and SP+AT arms, respectively; for PYR, these were 4.0 and 3.0 h, respectively. The AUC(0-288) of SDX were 15,840 and 18,876 microg/ml h for the SP and SP+AT arms, respectively; for PYR, they were 124 and 112 microg/ml h, respectively. The t ((1/2)) of values for SDX were 165 and 180 h for the SP and SP+AT arms, respectively; for PYR, these were 158 and 177 h, respectively. There was no statistically significant difference between the C(max), T(max), AUC(0-288) and t ((1/2)) between the two arms (p > 0.05). CONCLUSION: Taking AT concomitantly with SP does not have any impact in the disposition of SP.

Simple and cost-effective liquid chromatographic method for determination of pyrimethamine in whole blood samples dried on filter paper.

A cost-effective HPLC method for determination of pyrimethamine (PYR) in human whole blood samples dried on filter paper (Whatman) is reported. Trimethoprim (TMP) was used as an internal standard. Whole blood spiked with PYR was transferred (100 microl) onto filter paper and dried at room temperature. Capillary blood samples (100 microl) after ingestion of three tablets of sulfadoxine-pyrimethamine (SP) by one subject were also tested. PYR and an internal standard (IS) TMP were extracted into di-isopropyl ether as bases and then re-extracted with 150 microl mobile phase. A C-18 column was used and the mobile phase consisted of phosphate buffer (0.05 M, pH 5):acetonitrile:concentrated perchloric acid (750:300:2.5, v/v/v). The absorbances of PYR and IS were monitored at 270 nm. The limit of quantification was 40 ng/ml. The within- and between-assay coefficient of variations were <10% at the limit of quantification.

Assessing prescribing practice in church-owned primary healthcare (PHC) institutions in Tanzania: a pilot study.

A retrospective survey of prescribing patterns in 10 church-owned primary healthcare (PHC) institutions in Dar es Salaam region, Tanzania, was carried out by trained research assistants in order to assess the prescribing practices of healthcare providers in these institutions. From a total of 15,000 prescriptions, 600 were recorded randomly from patient registers retrospectively. This work was carried out between April to September 1996. Each prescription was recorded using World Health Organization Action Programme on Essential Drugs (WHO/DAP) forms and analysed manually. The average number of drugs per prescription was 2.9; the percentage encounters for injections and antibiotics was 38 and 71, respectively. Ninety-four per cent of all drugs were prescribed according to the essential drug list of Tanzania.

Evaluation of the quality of amodiaquine and sulphadoxine/pyrimethamine tablets sold by private wholesale pharmacies in Dar Es Salaam Tanzania.

OBJECTIVE: There are several independent reports in Tanzania of treatment failures with commercially available sulphadoxine/pyrimethamine (SP) and amodiaquine (AQ) brands. The aim of this work was to assess the quality of SP and AQ tablets marketed by wholesale pharmacies in Dar Es Salaam, Tanzania. METHODS: All eight wholesale pharmacies authorized to import medicines and located in Dar Es Salaam were included in the study. From each pharmacy, samples of all SP and AQ brands available at the time of sampling were bought, provided they had a shelf-life of at least 1 year. A sample was either an intact box of 100 tablets or a sealed tin of 100 tablets. To ensure blinding, 30 tablets of each sample were removed from their original containers, coded and sent to the quality control laboratory for analysis. The name, strength, batch number, manufacturer and the expiry dates of the tablets were recorded. In total 15 AQ and 18 SP samples were collected. Identity, assay for content of active ingredients and dissolution assay were performed as described in the United States Pharmacopoeia (USP). RESULTS: All samples passed the identity test. Among the AQ samples collected, two of 15 (13%) failed the dissolution test but all passed the assay for content, whereas two of 18 (11%) and eight of 18 (44%) SP samples failed the assay for content and dissolution tests, respectively. None of the pharmacies stocked all AQ and SP brands. CONCLUSION: This work reveals the availability of poor quality antimalarial drugs on the Tanzanian market. Use of substandard drugs could have serious clinical consequences to patients. The results support the need for continuous monitoring of the quality of marketed drugs to ensure safety and efficacy of these products in the treatment of malaria in endemic areas.

Comparative bioavailability of oral sugar-coated and plain formulation of chloroquine phosphate marketed in Tanzania.

The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight) of a sugar-coated (Dawaquin) and a plain formulation (Shellyquine) of chloroquine phosphate were compared in two groups of 10 volunteers each, following an overnight fast. Whole blood chloroquine concentrations were measured using high-performance liquid chromatography (HPLC) and bioavailability was determined by measuring area under the blood chloroquine concentration curve (AUC ng mL(-1) h) and the peak blood chloroquine concentration (Cpmax ng/mL). The AUC and Cpmax for Shellyquine were 4396.3 +/- 833 ng mL(-1) h and 162 +/- 14 ng/mL, respectively. The AUC and Cpmax for Dawaquin were 2060 +/- 339 ng mL(-1) h and 56.6 +/- 5.2 ng/mL, respectively. Shellyquine was significantly more bioavailable than Dawaquin (P<0.001). Although the Cpmax for Dawaquin was higher than the required therapeutic level for sensitive Plasmodium falciparum of 30 ng/mL, its blood levels may not guarantee a rapid clearance of parasites. The differences between the two formulations point to a problem in the quality of pharmaceuticals marketed in this country, whose extent need to be ascertained further. Failure of chloroquine phosphate in this country has already been declared by the Ministry of Health, and the potential contribution of poorly formulated products remains a subject of debate.

Comparative in vitro and in vivo study of a sugar-coated chloroquine preparation marketed in Tanzania versus an ordinary brand.

OBJECTIVE: To investigate the absorption and the quality of a sugar-coated chloroquine (CQ) marketed in Tanzania. METHOD: Twenty healthy volunteers were randomised to take either the test brand (group A) or a control chloroquine phosphate (group B). Each subject received 300 mg chloroquine base. Whole blood dried on filter papers were collected at time 0 and at 15 and 30 min and at 1, 2, 3, 4, 6, 8, 24, 36, 48, 72 and 168 h after drug intake. Urine samples were collected at time 0, 0-4 h, 4-8 h, 8-24 h, 24-48 h and 48-72 h after drug administration. In an in vitro study, six tablets from each of the two CQ preparations were checked for the amount of active drug contained in each tablet and their dissolution rates. RESULTS: The blood concentration Area Under the Curve (AUC) of group B was about 10% larger than that of group A. The total amounts of CQ plus deethylchloroquine excreted with the urine during the 72-h study period were 5% for group A and 6% for group B. None of the pharmacokinetic parameters were significantly different between the two groups. All the tablets contained the labelled amount of chloroquine; however, one tablet from the test drug failed to fulfil the required dissolution rate. CONCLUSION: We found no major difference between the AUCs of the two CQ preparations, but the sugar-coated brand has shown to have variable dissolution rate.

Prescribing habits in church-owned primary health care facilities in Dar Es Salaam and other Tanzanian coast regions.

OBJECTIVE: To assess prescribing practice of Primary Health Care (PHC) workers in church owned health care facilities using WHO drug use indicators. DESIGN: A cross-sectional study in which twenty primary health care facilities were randomly selected. Prescribing indicators were obtained by analysing outpatient records retrospectively for the past 14 months between January 1997 and February 1998. This period was chosen because of compete records of outpatient attendances. Patient care and facility indicators were recorded prospectively during the study period. SETTING: The study was conducted in the Coast and Dar es Salaam regions of Tanzania. Six districts were randomly selected from both regions. The selected districts included Ilala, Temeke and Kinondoni in Dar es Salaam, Kibiti, Bagamoyo and Kisarawe in Coast region. SUBJECTS/MATERIALS: Twenty primary health care facilities were randomly selected from the chosen districts. Patient registers were collected and patients' characteristics including age, sex, diagnosis, and drugs prescribed for the period January 1997 to February 1998 were recorded on data collection forms. Patient care indicators were measured by recording consultation time, dispensing time, per cent of drugs actually dispensed and adequately labelled whereas patients' knowledge of correct drug dosage was obtained using exit interviews. Verification of facility indicators was done by direct observation. RESULTS: The average number of drugs per prescription was 2.3 (range 1.8-2.8). Generic prescribing prevailed with a mean of 75.5% of all drugs. Antibiotic and injection encounters per prescription was 35.4 and 19%, respectively. Most drugs were prescribed according to the essential drug list of Tanzania (NEDLIT). Patient's average consultation time was 3.6 minutes whereas average dispensing time was 39.9 seconds. On average, 87% of all drugs dispensed were adequately labelled and patients' knowledge of correct dose was adequate. All facilities possessed drugs for treating important illnesses, all had reference educational materials. CONCLUSION: The study shows that there is an overuse of injections 19% +/- 1.7 (range 0.73%) compared to the recommended figure of 15%. The use of antibiotics appears appropriate when compared with the morbidity patterns in the study areas. A focus group discussion with prescribers in these facilities to address the question of overuse of injections is needed in order to plan an appropriate intervention.

Slow chloroguanide metabolism in Tanzanians compared with white subjects and Asian subjects confirms a decreased CYP2C19 activity in relation to genotype.

BACKGROUND: We have previously found decreased CYP2C19 activity in Tanzanians tested with mephenytoin and omeprazole in relation to genotype when compared with white and Asian subjects. OBJECTIVE: We investigated the impact of CYP2C19 genotype and phenotype on chloroguanide (INN, proguanil) metabolism to its metabolites cycloguanil and 4-chlorophenylbiguanide. METHODS: A single oral chloroguanide dose was given to 25 healthy Tanzanian subjects with CYP2C19 genotypes (CYP2C19*1, CYP2C19*2, and CYP2C19*3). Homozygous wild-type and mutated genotype groups were chosen randomly, but the heterozygous genotype group was chosen with a range in phenotype. We used a novel HPLC method for drug determination. RESULTS: Pharmacokinetics of chloroguanide did not differ between groups. Maximum plasma concentration (Cmax) and area under the plasma concentration versus time [AUC(0-infinity)] for cycloguanil was significantly lower (t test P < .05) in the homozygously mutated group compared with the homozygously wild-type group. There were similar significant group differences of median urinary excretion. The chloroguanide/cycloguanil ratio closely correlated (r(s) = .87) with omeprazole metabolic ratio, confirming that Tanzanian subjects are generally slower CYP2C19 metabolizers. It also confirms that CYP2C19 genotype and phenotype predicts cycloguanil formation. In addition, a 3-hour plasma sample metabolic ratio also seems to be a proper time for omeprazole phenotyping in Tanzanian subjects. Because the plasma concentrations of cycloguanil and 4-chlorophenylbiguanide covary (r(s) = .89), it is now suggested that their formation be catalyzed by the same enzyme (ie, CYP2C19) through a common intermediate, the structure of which is also presented. CONCLUSIONS: As shown in an earlier study, also with a third substrate, Tanzanians have a lower capacity to form cycloguanil than white and Asian subjects. Individuals with two mutated alleles have lower metabolic capacity than individuals with two wild-type alleles or individuals in the heterozygous group, which may lead to chloroguanide therapeutic failure. This knowledge should be important when selecting appropriate patients and doses of chloroguanide in different populations.

Decreased capacity for debrisoquine metabolism among black Tanzanians: analyses of the CYP2D6 genotype and phenotype.

The cytochrome P450 2D6 (CYP2D6) genotypes and phenotypes of 106 unrelated, healthy black Tanzanians of Bantu origin were investigated. The results revealed a population with a generally decreased capacity to metabolize the CYP2D6 substrate debrisoquine with 59% of the Tanzanian extensive metabolisers having debrisoquine metabolic ratios (MRs) > 1 versus 20% in Caucasians. This decrease in metabolic capacity was not fully explained by the partially or fully detrimental CYP2D6 gene mutations analysed for in this study. As many as 7% poor metabolizers of debrisoquine were identified but none was homozygous for defective CYP2D6 alleles. The majority among the group of poor metabolizers had relatively low metabolic ratios. The mutational profile indicated a closer association of the Tanzanian CYP2D locus to that of Zimbabweans rather than to that of Ethiopians. The defective alleles CYP2D6*3, *4, *5 and *6 were found at low frequencies (0%, 1%, 6%, 0%, respectively), whereas the CYP2D6*17 allele causing an enzyme with altered specificity was common (allele frequency = 17%). It is concluded that the CYP2D6 genotype in the Tanzanian Bantu population is different from that of other African populations examined to date and that further studies are required to explain the generally lower capacity to metabolize CYP2D6 substrates.

Bantu Tanzanians have a decreased capacity to metabolize omeprazole and mephenytoin in relation to their CYP2C19 genotype.

OBJECTIVE: To investigate the CYP2C19 polymorphism in Tanzanians because this enzyme shows large interindividual differences in activity and metabolizes several drugs of importance in Africa, especially the antimalarial agent chloroguanide (INN, proguanil). METHODS: Two hundred fifty-one Tanzanian healthy volunteers were phenotyped with respect to CYP2C19 with use of a single oral dose of mephenytoin (n = 106), a single oral dose of omeprazole (n = 207), or both. Sixty-two were phenotyped with both probe drugs. The urinary 0- to 8-hour S/R-mephenytoin ratio and the plasma omeprazole metabolic ratio (MR) (omeprazole/hydroxyomeprazole) 3 hours after drug intake were determined. The genotype was determined by analysis for CYP2C19*1 (wt), CYP2C19*2 (m1), and CYP2C19*3 (m2). Ten subjects with high omeprazole MR were screened for new mutations in the CYP2C19 gene by searching for single-strand conformation polymorphisms (SSCP). RESULTS: Eight subjects were classified as mephenytoin poor metabolizers (7.5%). Only 5 of these were homozygous for mutated alleles. The S/R ratio was skewed to the right (lower CYP2C19 activity) compared with other ethnic groups studied previously. No new mutations were found with polymerase chain reaction (PCR)-SSCP. We found 30 volunteers (14.5%) with an MR > 7, which is the antimode found previously in white subjects and Asian subjects. Of the 251 volunteers genotyped, 3.2% were homozygous for mutated alleles and 66.1% were homozygous for the wild-type allele. The allele frequencies of CYP2C19*1, *2, and *3 were 81.5%, 17.9%, and 0.6%, respectively. The correlation between the S/R-mephenytoin ratio and the omeprazole MR was significant (Spearman r = 0.59; P < .01). CONCLUSION: Tanzanians have a decreased capacity to metabolize both omeprazole and mephenytoin when their genotype is compared with metabolic capacity and genotype in other previously studied populations. We identified a low frequency of the Asian allele (CYP2C19*3). Although we did not find any new mutations, our results may be consistent with the presence of yet-unidentified mutations of CYP2C19 that causes decreased CYP2C19 activity in the Tanzanian population.

Comparison of drug utilisation in public and private primary health care clinics in Tanzania.

A study was carried out in 20 public and 20 private out patient clinics (dispensaries) in Dar es Salaam. At least 30 prescriptions were collected from each clinic. A total of 1200 were collected for analysis. Prescribing indicators from the WHO/DAP "how to investigate drugs in health facilities" were used. The average number of drugs per prescription in public clinics was 2.2 compared to 2.5 in private ones (p > 0.05). The percentage generics was 51.7 in public clinics against 47.7 in private (p > 0.05). On the other hand the percentage of antibiotics was 12.3 in public against 19.7 in private (p < 0.05) whereas injections percentage was 9.6 in public against 12.7 in private clinics (p < 0.05). The results suggest a need for intervention to curb the irrational use of antibiotics and injections in private clinics.

Chloroquine blood concentrations and malaria prophylaxis in Tanzanian women during the second and third trimesters of pregnancy.

OBJECTIVE: Routine malaria prophylaxis with chloroquine (CQ) is recommended to pregnant semi-immune women in several countries in Africa. The dosage is empirically based. We investigated whether blood CQ concentrations and apparent oral blood clearance (CL/F) change during the course of pregnancy. We also studied whether malaria parasites could be detected together with low CQ blood levels. METHODS: Forty nine semi-immune Tanzanian women were recruited in the 16th week of pregnancy. They were given 310 mg oral CQ base once per week as prophylaxis during the whole pregnancy. Capillary blood samples were taken for analysis of CQ before treatment and at weeks 26 and 36. Blood samples were dried on filter paper and analysed by HPLC. Blood was also drawn to detect occurrence of malaria parasites. RESULTS: A total of 25 women fulfilled the sampling schedule. CL/F increased significantly from 160 ml.min-1 at week 26 to 180 ml.min-1 at week 36. In 7 of 25 women, CL/F increased > 20%. Trough blood CQ concentrations, determined on four occasions at week 26 and at week 36 varied between 200 and 900 nmol.l-1. No statistically significant differences between occasions were seen. Malaria parasites were seen in two individuals early in pregnancy. CONCLUSION: Blood CQ CL/F showed a small increase during the course of pregnancy. The estimated mean blood CL/F values of 160 and 180 ml.min-1 (week 26 and 36, respectively) were higher than the mean CL/F of 125 ml.min-1 in non-pregnant individuals, published previously. Efficacy of higher dosages of CQ in malaria prophylaxis in pregnant women could, therefore, be evaluated in controlled trials in high-risk malaria areas.

Utilisation of antimalarial drugs by pregnant women attending the antenatal clinic at Muhimbili Medical Centre, Dar es Salaam.

Two hundred women in early second trimester were recruited in a study to monitor the utilisation of antimalarial drugs prescribed for prophylaxis or treatment of malaria during their attendance at the antenatal clinic of Muhimbili Medical Centre. Information regarding the use of antimalarial drugs was obtained during an interview using a structured questionnaire and antenatal cards. The study revealed that 51.5% had taken antimalarials for treatment of acute malaria while 23.5% had taken for prophylaxis. There was thus a total exposure of 75%. most of them were exposed to choloroquine (69.5l%). There was no statistically significant association between the taking of chloroquine and its presence in urine and between the level of education and the taking of chloroquine prophylactically.

Brine shrimp bioassay for biological activity of medicinal plants used in traditional medicines in Tanzania.

A method utilizing Brine Shrimp (Artemia salina Leach) has been used to screen medicinal plants for biological activity. A number of twenty eight medicinal plants were collected from eastern part of Tanzania and their ethnobotanical uses obtained from traditional healers. Biological activity using the Brine Shrimp bioassay was recorded as a lethal concentration (LC 50) that kills 50% of the larvae within 24 hours of contact with the methanol plant extract. Of the 28 plant extracts tested eight gave an LC 50 of activity of less than 20 mu g/ml when compared with controls treated with 10% dimethylsulphoxide (DMS0) in water as solvent. Uvaria acuminata (Annonaceae) root extract was found to be the most active. The Brine Shrimp bioassay was found to be reliable, inexpensive and a convenient method for assessment of biologically active medicinal plants.

A study of prescribing patterns at different health care facilities in Dar es Salaam, Tanzania.

A survey of outpatient prescriptions in three district hospitals, four health centres, and ten dispensaries in Dar es Salaam region has been undertaken, and the significance of the data especially as it relates to prescribing patterns is discussed. The data indicate that the average number of items (drugs) per prescription in hospitals, health centres, and dispensaries was 2.4 +/- 0.16, 2.1 +/- 0.5, and 1.9 +/- 0.2 (+/- SD) respectively, while injections accounted for 18, 20, and 32 percent of all prescriptions in hospitals, health centres and dispensaries respectively. On the other hand, antibiotics accounted for 40, 35 and 36 percent of all prescriptions in hospitals, health centres and dispensaries respectively. Generic prescribing was very high in all health facilities and accounted for approximately 80% of all prescriptions. Prescriptions containing fixed drug combinations were not common.

Knowledge and management of malaria in Dar es Salaam, Tanzania.

A study of knowledge and management of malaria was undertaken prospectively in 20 dispensaries, 20 drug stores, 120 patients attending dispensaries and 120 customers at drug stores in Dar es Salaam, Tanzania. This was a descriptive study where two different questionnaires were developed and administered to the target groups in oral interview. All the respondents were aged 14 years and above. The results of the interview showed that the knowledge of rural medical aides (RMA's) on signs and symptoms of malaria and which drugs cure malaria was satisfactory. However, only 65% of the RMA's could remember the correct dose of chloroquine for an adult. Although the knowledge of drug sellers on signs and symptoms of malaria was adequate, 45% of them did not know the correct dose of chloroquine. In view of the fact that only 30% of patients and 20% of shoppers knew the correct dose of chloroquine for adults, it appears that their management of malaria is inadequate. To improve the management of malaria at dispensary and drug store level, there is a need to introduce treatment charts and/or guidelines and the Ministry of Health should promote health education to the public.

PIP: In early 1992 in Tanzania, trained research assistants interviewed 20 rural medical aides (RMAs), 20 drug sellers, 120 patients at 20 dispensaries, and 120 customers of drug stores, all in Dar es Salaam, to examine knowledge and practices of health workers, drug sellers, and patients concerning malaria. The RMAs had adequate knowledge of the signs and symptoms of malaria (e.g., 90% for fever, 85% for headache, and 80% for painful joints). The drug sellers also had adequate knowledge of signs and symptoms (e.g., 80% for fever, 45% for headache, and 50% for painful joints). Even though chloroquine-resistant strains of Plasmodium falciparum malaria exist in Tanzania, all RMAs and most drug sellers (85%) believed that chloroquine could cure malaria. Further, it is the only antimalarial that the Ministry of Health provides its dispensaries. Just 65% of RMAs knew the correct dosage of chloroquine for people 14 years old and older. An even lower percentage of drug sellers knew the correct dosage (50%). Just 33.7% of patients and 22.5% of customers knew the correct dosage of chloroquine. An inadequate supply of chloroquine was available at 15% of dispensaries and 30% of drug stores. RMAs sometimes gave patients too few chloroquine tablets for a full course of therapy. Other drugs mentioned by RMAs to treat malaria were quinine, amodiaquine, cotrimoxazole, halofantrine, pyrimethamine/sulphalene, and pyrimethamine/sulphadoxine. Those mentioned by drug sellers included aspirin plus chloroquine, cotrimoxazole, pyrimethamine/sulphadoxine, and traditional medicines. These findings suggest that irrational drug therapy of malaria promotes resistant strains and prolongs the duration of illness. Introduction of treatment charts and health education promotion to the public are needed to improve malaria management at dispensaries and drug stores.

A study of prescribing patterns with special reference to drug use indicators in Dar es Salaam Region, Tanzania.

Drug prescribing patterns were studied in 720 retrospective and 779 prospective outpatient prescriptions from 20 dispensaries in Dar es Salaam region, and these revealed a mean drug exposure of 2.0 and 2.3, respectively. The percentage of patients leaving the dispensaries with no prescribed drugs was 1.3% and 0.7%, respectively. Prescriptions containing antibiotics were 36.8% (retrospective) and 39.8% (prospective), while injections accounted for 24.6% and 34% of the total encounters, respectively. Over 70% of prescriptions conformed to the Tanzania essential drug list (EDP) and/or standard treatment guidelines and consisted of 83.9% and 79.1% generic prescriptions, respectively. Interestingly, only 15% of the surveyed dispensaries had an EDP book and/or calendar. Despite the consulting and dispensing times being short (2.98 min and 77.7 s, respectively), 70% of the patients could remember the dosing instructions. Only 64% of the patients had a minimum physical examination.

The pharmacological actions of a crude aqueous extract of khat (MIRAA) on rabbit's duodenum and heart in vitro

In this study a crude aqueous extract from fresh leaves and twigs of khat (Miraa) was investigated for its effects in vitro on rabbit's doudenum and perfused heart preparation. There was a significant reduction in spontaneous contraction of the duodenum in the presence of increasing doses of khat extracts. On the rabbit's heart; khat caused an inhibition of spontaneous contractions. It is therefore suggested that chronic habitual abuse of khat may predispose to gastrointestinal and cardiovascular problems in human subjects

The bioavailability of chloroquine in healthy adult volunteers

It is recommended that for individuals weighting 45 to 55kg a dose of chloroquine of 600mg on first day 300mg on second day and 150mg on third day would give desired therapeutic non-toxic levels whereas for heavier individuals (80-90kg) the appropriate dosage would be 5 tablets (750mg) first day; 4 tablets (600mg) second day and 3 tablets (450mg) on third day