Efficacy of a loading dose of oral chloroquine in a 36-hour treatment schedule for uncomplicated plasmodium falciparum malaria.

The efficacy of a loading dose of 20 mg of chloroquine per kg of body weight per os given at intervals during the first day was evaluated in 27 patients in Madagascar with Plasmodium falciparum malaria. The conventional regimen of 25 mg/kg over 3 days (schedule 1) was thus compared with a regimen of 30 mg/kg over 2 days (schedule 2; one dose of 10 mg/kg followed by two doses of 5 mg/kg at 6-h intervals on the first day and two doses of 5 mg/kg at 12-h intervals on the second day) in terms of their clinical and parasitological efficacies, tolerance, and drug concentration-time curves. At 24 h schedule 2 gave higher chloroquine levels in blood, which induced a more rapid decrease in parasitemia.

Effect of food on the absorption of vigabatrin.

1. This study, involving eight healthy volunteers, revealed that food intake does not have a clinically significant effect on vigabatrin kinetics. 2.

Clinical evaluation of the cardiovascular effects and the pharmacokinetics of benalfocin and its metabolite in healthy subjects during repeated dosing.

The cardiovascular effects and the pharmacokinetics of a new selective alpha-2 adrenoceptor antagonist, benalfocin, and its active metabolite, both compounds with a similar receptor affinity profile, were examined in healthy volunteers during repeated dosage. Significant diastolic blood pressure lowering effects were observed on the first and the last day of the treatment persisting throughout the dosage interval. Furthermore, heart rate reductions were found on these days which were significantly correlated with both the parent compound's and the metabolite's plasma concentrations and their sum.

Exercise during therapeutic beta-blockade: a two-year study in hypertensive patients.

The use of beta-adrenoceptor blocking drugs has been thought to impair physical performance. To test this statement, 12 patients with mild to moderate hypertension performed a submaximal exercise test during treatment with placebo and after 3 and 24 months of monotherapy with betaxolol, 20 to 40 mg daily. The resting heart rate and systolic and diastolic blood pressures were reduced after 3 months of treatment and the reduction was maintained 24 hours after the last dose at the 2-year visit.

Effect of beta 1-selective and non-selective beta-blockade on work capacity and muscle metabolism.

Six well-trained men were studied while performing a maximal bicycle exercise. The seven experiments included in this study were randomized in a double-blind cross-over fashion. On each occasion the subjects were given either placebo or 40, 80, or 160 mg propranolol (non-selective blockade) or 25,50, or 100 mg atenolol (beta 1-selective blockade).

Concentration-dependent blood pressure effects of guanfacine.

Central alpha 2-adrenoceptor stimulation decreases blood pressure, whereas stimulation of postjunctional peripheral adrenoceptors induces a pressor response. The net blood pressure response during multiple dosing is the sum of these effects and is dependent on drug kinetics, receptor affinity, and receptor occupancy. Guanfacine (2 to 6 mg/day), a selective alpha 2-adrenoceptor agonist, decreased blood pressure in patients with hypertension.

Haemodynamic and metabolic responses to prolonged exercise after chronic beta 1-adrenoceptor blockade in hypertensive man.

The influence of chronic beta 1-adrenoceptor blockade on haemodynamic and metabolic responses was examined in eight young hypertensive subjects during a 40 min submaximal bicycle test at 50% of maximal capacity. The patients were randomly allocated to one placebo and one treatment period of 6 weeks. During treatment atenolol (Tenormin, 100 mg) was given twice daily.

Further support for changes in chloroquine disposition and metabolism between a low and a high dose.

The kinetics of chloroquine and its major metabolite desethylchloroquine were studied in patients with rheumatoid disease after single oral doses of chloroquine phosphate corresponding to 150 and 300 mg chloroquine base. The findings strengthen the previous finding that the disposition of chloroquine involves rate limiting steps.

Arterial blood pressure and general sympathetic activation in essential hypertension during stimulation.

We asked whether exaggerated blood pressure (BP) reactivity in patients with essential hypertension (HT) is a sign of specific activation of the cardiovascular system or of generalized sympathetic activation. Fourteen patients with essential hypertension and 14 matched normotensive (NT) controls were subjected to tasks involving attentional demands, mental arithmetic, a cold pressor test and isometric muscular contraction. Systolic and diastolic BPs, skin and muscle blood flows, heart rate, skin conductance level and fluctuations during each task were recorded.

Therapeutic and metabolic effects of sotalol.

In a single-blind, randomized study, the cardiovascular and metabolic effects of sotalol, 40 to 160 mg/day, in six patients with mild essential hypertension were compared to those of placebo at rest and during submaximal dynamic exercise. Resting blood pressure was controlled by sotalol but not the pressor response to exercise, despite reduction of tachycardia. The major metabolic finding on sotalol was an approximately 40% decrease in lipid mobilization during exercise.

Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension. Demonstration of a therapeutic window in man.

Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 micrograms/kg to patients with essential hypertension (n = 6).

The single dose kinetics of chloroquine and its major metabolite desethylchloroquine in healthy subjects.

The kinetics and disposition of chloroquine (CQ) and its metabolite monodesethylchloroquine (CQM) were investigated in 5 healthy volunteers after incremental (150-300-600mg CQ base) single oral doses of CQ. The analytical method used (HPLC and fluorescence detection) is the most sensitive known method for CQ and CQM. Plasma and whole blood concentrations of CQ, CQM and a third metabolite, bidesethylchloroquine (CQMM), were determined.

Effect of clonidine at steady state on blood pressure in spontaneously hypertensive rats. Interaction of various alpha-adrenoceptor antagonists.

The influence of various alpha-adrenoceptor antagonists (phentolamine, yohimbine, R 28935, prazosine, terazosine) on clonidine's blood pressure effects at different steady state plasma concentrations was investigated in awake spontaneous hypertensive rats. Clonidine's threshold (greater than 10 mmHg, less than 20 mmHg) antihypertensive effect was potentiated by phentolamine but opposed by centrally acting antagonists as was the maximal antihypertensive effect. The pressor response on the other hand was blocked by peripherally acting alpha-1- and alpha 2-antagonists.

Muscle fibre composition in relation to blood pressure response to isometric exercise in normotensive and hypertensive subjects.

A positive relationship was demonstrated between the blood pressure and the fibre composition of the vastus muscle at rest in 17 hypertensive and 17 age- and sex-matched normotensive subjects. The hypertensive group had a higher proportion of fast twitch (FT) fibres (p less than 0.1).

Steady state disposition of chloroquine in patients with rheumatoid disease.

The steady state disposition of chloroquine and its major metabolites, monodesethyl and bidesethyl chloroquine, were determined in 6 patients on long-term treatment for rheumatic disease with 99-155 mg base/day. The total body clearance of chloroquine was 0.35 l/kg/h and that of its metabolites was much higher.

Haemodynamic and electrodermal correlates of psychogenic stimuli in hypertensive and normotensive subjects.

This study compared tonic and phasic cardiovascular and electrodermal activity in subjects having essential arterial hypertension (HT) with that of sex- and age-matched normotensive (NT) controls. Fourteen subjects of each group were subjected to 'sensory intake' (letter identification) and 'rejection' (mental arithmetic) tasks while recordings were made of: systolic and diastolic arterial blood pressure, hand and forearm blood flows, heart rate, skin conductance level and fluctuations. The rejection task affected more physiological variables in both groups than the intake task did.

Clonidine kinetics in man--evidence for dose dependency and changed pharmacokinetics during chronic therapy.

1 Clonidine kinetics were studied in 21 patients with essential hypertension. All received two bolus i.v.

Metabolic effects in muscle during antihypertensive therapy with beta 1- and beta 1/beta 2-adrenoceptor blockers.

The hemodynamic and metabolic consequences of long-term antihypertensive treatment with beta 1- and beta 1/beta 2-adrenoceptor blockade was investigated in five young men with mild essential arterial hypertension (World Health Organization stages I and II) at rest and during submaximal exercise in a single-blind crossover study. The drugs (atenolol and alprenolol) were given in equipotent doses as estimated from their effects on blood pressure. Leg blood flow and oxygen uptake were the same during both treatment periods.

Leg blood flow during exercise in man in relation to muscle fibre composition.

Fibre composition in the vastus lateralis muscle, leg blood flow, oxygen uptake and respiratory exchange ratio were determined in 12 healthy male volunteers during submaximal exercise (50% of V02 max). The percentage of slow-twitch fibres varied from 26 to 66. Mean leg blood flow during exercise was 4.