The disposition of amodiaquine in Zambians and Nigerians with malaria.

1. Oral amodiaquine (AQ) has been used to treat patients with symptomatic malaria in Zambia (n = 14) and Nigeria (n = 5). Clinical cure was obtained in all patients and no serious adverse drug reactions were seen. 2. As in healthy subjects, AQ achieved low plasma concentrations. Plasma concentration vs time profiles of desethylamodiaquine (AQm) from the present study did not differ from those obtained from healthy subjects. 3. In contrast to previous results from healthy subjects, the mean ratio of red cell (RBC): plasma AQm concentration in the present study was 0.80: 1 at the start of the study and rose in a linear manner (r = 0.873; P less than 0.01) to 3.04: 1 by the end (n = 10; P less than 0.01). The final mean value was similar to that seen in healthy subjects. 4. These data show that there are differences in the disposition of orally administered AQ between healthy subjects and patients with clinical malaria. The relevance of this observation to the frequency of adverse reactions to AQ in these two groups is not established.

Management of clinical trials in developing countries.

PIP: Clinical trials need to consider specifics in trial circumstances when novel measures to improve health call for assessment in developing countries. Predictions regarding safety and efficacy under regional conditions, deriving from data of trials in affected populations in another part of the world, cannot always be accepted as reliable indicators of future regional performance. The primary objective should be to reveal new information. This discussion of the management of clinical trials in developing countries focuses on the following: the protocol; staff and supervision; locations and logistics; the use of a pilot study; drugs and compliance; and ethics. At an initial workshop a planning group with the broadest possible representation draws up a protocol. Ideally, the protocol is never imposed but is developed through extensive consultation and coordination. Its initial objective is an agreement on how to make a specific study feasible. Initial goals should be restricted to answering a few simple but meaningful questions. Information in the study protocol includes: aims and objectives; precise definitions of clinical variables; detailed description plus frequency and timing of clinical procedures, laboratory tests, and so forth; case report forms; consent forms and any warning notices written in the local language; work manuals for the pharmacist of drug supervisor; the treatment allocation procedure and individual treatment charts; the labeling code, emergency code breaking, and referral procedures; precise guidelines for evaluation and management of known adverse reactions; and an investigational data brochure. Selection of a competent, dependable, and enthusiastic principal investigator, available for the full duration of the study is essential. Suitable trial sites should be carefully chosen to avoid conditions that might prevent application of adequate scientific standards. In case of doubt about the logistical feasibility, starting with a trial run of the test procedures or with a pilot study using an established drug should be considered in order to detect potential problems concerning availability of scientific and technical expertise, equipment or reagents. It is necessary to check national clearances for investigating new agents. Permits may be required from a review body, a manufacturer, or from an authority. All needed drug supplies should be obtained at once together with information on stability under expected storage conditions. An independent measure of patient compliance needs to be agreed upon. Projects should be reviewed as well as approved by an independent local group, practicing the highest standards of protection of the rights of the individual. Data collection begins with identification of subjects, by photographs of faces, in addition to careful records of name, household, domicile, and occupation.^ieng

A double-blind comparative clinical trial of mefloquine and chloroquine in symptomatic falciparum malaria.

A total of 99 male Zambian patients with symptomatic falciparum malaria were treated in a double-blind randomized manner with either mefloquine (1000 mg given in one day) or chloroquine (1500 mg given over 3 days). An S-type response was seen in all the chloroquine patients and 98% of the mefloquine group; one patient in the latter group (2%) showed an RI-type response, but the parasites obtained during the recrudescence were sensitive to both chloroquine and mefloquine in the in vitro microtest, and the patient responded satisfactorily to oral chloroquine. The rate of clearance of parasitaemia was marginally faster in the chloroquine-treated group. The rate of clearance of fever was similar in the two groups. Both drugs were well tolerated and side-effects such as nausea, vomiting, dizziness, loose stools, and pruritus were mild and transient. Pruritus was more common after chloroquine administration and dizziness more common in the mefloquine group. There were no drug-induced alterations in the haematological and biochemical profiles.

Comparison of the effects of propranolol and MJ 1999 on cardiac beta-adrenoceptors in man.

1. Propranolol, a beta-adrenoceptor blocking drug with local anaesthetic and a direct myocardial depressant action, and MJ 1999, a beta-adrenoceptor blocking drug which has no local anaesthetic or intrinsic sympathomimetic action, were compared for beta-adrenoceptor blocking activity in man.2. Propranolol was 2.67 times more active than MJ 1999 in reducing by 50% the tachycardia produced by the intravenous infusion of isoprenaline in healthy volunteers.3. Propranolol and MJ 1999 intravenously both reduced resting heart rate in the standing position and an exercise tachycardia, but there was no qualitative or quantitative difference between them.4. On oral administration, both propranolol and MJ 1999 reduced resting heart rate and an exercise induced tachycardia; propranolol was only slightly more active than MJ 1999.5. In patients with thyrotoxicosis propranolol was about twice as active as MJ 1999 in reducing the heart rate.