Oral single dose kinetics of mefloquine was investigated in 16 male volunteers, 3 Caucasians and 13 African natives. Unchanged mefloquine (= M) and one of its metabolites (= MM) were measured in the plasma. The apparent half-life of absorption of M ranged from 0.36 to 2.0 h, its terminal half-life of elimination from 15 to 33 days. Assuming complete systemic availability, an apparent volume of distribution of 14–29 liters kg-1 and a total clearance of 18–39 ml min-1 were derived. MM given orally to mice or rats showed at equal dose the same tolerance as mefloquine. Following oral administration of M to man, plasma levels of MM surpassed those of M, resulting in a 2.4–5.1 larger AUC. However, because of its much smaller apparent volume of distribution, MM may be anticipated to represent only a small percentage of the dose and therefore to contribute only to a minor extent towards the unwanted side effects of the drug.
1315We are grateful to Dr J Stevenson and Dr E C Gordon Smith for allowing us to report this case.'Perillo RP, Pohl DA, Roodman ST, Tsai CC. Acute non A non B hepatitis with serum sickness-like syndrome and aplastic anaemia. JAMA 1981 ;245:494-6 Conversiotn: SI to traditional iuits-viscosity of plasma and whole blood: I mPa s I cP.30"', increase in fetal blood viscosity, this rise being compounded of a 120%increase in packed cell volume and an 18% fall in erythrocyte deformability.Neither plasma viscosity nor plasma fibrinogen values were altered. The mean birth weight was 318 g lower in infants born to smoking mothers. CommentMaternal cigarette smoking in pregnancy results in changes in fetal blood viscosity and its major determinants similar to those described in non-pregnant adult smokers.3 When adult smokers become pregnant the large physiological variations in blood viscosity factors obscure the effects of smoking in maternal blood5 but not so in the fetus. In the extensive capillary microcirculation of the fetal placental villi, raised blood viscosity and reduced erythrocyte deformability would be apt to reduce blood flow significantly in accordance with Poiseuille's law. Reduced intravillous perfusion would combine with reduced intervillous blood flow on the maternal side of the placenta, owing to the effects of nicotine, and with the already reduced oxygen availability in both maternal and fetal blood, to cause fetal hypoxia stimulating fetal erythropoiesis with a further increase in blood viscosity leading to a vicious circle of decreasing flow and further hypoxia. This study indicates a new pathogenic pathway for the deleterious effects of maternal cigarette smoking on fetal growth and development in pregnancy. Recently, chloroquine resistant Plasmodium falciparum has been acquired in east Africa by white visitors.' 2 We have carried out more than 25 successful in vitro macrotests, 15 in vitro microtests using capillary blood specimens, and 130 in vivo tests on the susceptibility of P falciparum in Zambia to chloroquine and to the new antimalarial drug mefloquine.3-5 In the in vivo tests the patients were observed in an environment free of mosquitoes for 28-63 days after they developed malaria. Our results showed that P falciparum in Zambia is generally sensitive to standard doses of chloroquine or mefloquine.Here, however, we report perhaps the first proved case of chloroquine resistant Pfalciparum in an African living in Africa.Case report A 26 year old Zambian staff nurse developed clinical malaria, which was confirmed microscopically to be due to asexual P falciparum, one month after she had moved to a village 1000 km north east of Ndola. She was treated on 10 June 1982 with two doses of 200 mg chloroquine intramuscularly at an interval of eight hours. She refused a further injection of chloroquine the next day and instead took 600 mg amodiaquine by mouth. Her clinical condition improved for four days, during which time she returned to Ndola. For the next 10 days she felt slightly unwell with feve...
Summary1. The intravenous injection of isoprenaline, orciprenaline, salbutamol and isoetharine increased heart rate in anaesthetized dogs. Log dose-response curves obtained with a series of doses of salbutamol and isoetharine were flatter than those for isoprenaline and orciprenaline. The order of activity of the drugs in increasing heart rate was isoprenaline, orciprenaline, and salbutamol = isoetharine.2. The injection into the external iliac artery of isoprenaline, orciprenaline, salbutamol and isoetharine produced dose dependent increases in femoral blood flow. Log dose-response curves for all drugs were parallel. The order of activity of the drugs was isoprenaline, salbutamol=isoetharine and orciprenaline. 3. Salbutamol and isoetharine were less active than orciprenaline in increasing heart rate but more active in increasing femoral blood flow. 4. These observations indicate that salbutamol and isoetharine have a greater effect on P2 than on 13-adrenoceptors in the cardiovascular system.
Summay1. Propranolol, a 3-adrenoceptor blocking drug with local anaesthetic and a direct myocardial depressant action, and MJ 1999, a P-adrenoceptor blocking drug which has no local anaesthetic or intrinsic sympathomimetic action, were compared for f8-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.
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