A method has been developed for the rapid quantitative analysis of chloroquine and its metabolite desethyl-chloroquine in plasma, blood and urine using high-performance liquid chromatography. An ethylene dichloride extract of the alkalinized biological samples was extracted with dilute acid and chromatographed on a reversed-phase column. Phosphate buffer in acetonitrile was used as the mobile phase with perchlorate as the counter-ion. Ultraviolet absorption at 254 or 340 nm or fluorescence detection was used. The fluorescence spectra and the fluorescence quantum yield of the substances were determined. Chloroquine and desethyl-chloroquine concentrations in the range of 10 nmol/l (UV-detection) and of 0.5 nmol/l (fluorescence detection) could be accurately measured with a relative standard deviation of 12%. The method should be adequate for therapeutic and pharmacokinetic studies.

The therapeutic efficacy of clonidine as an antihypertensive in a b.i.d. schedule 150--300 micrograms daily was evaluated. The blood pressure reduction in patients with essential hypertension was satisfactory on this regimen and the steady-state plasma concentrations were within the BP-lowering concentration range at the end of a dosage interval.

1 Clonidine kinetics were studied in 21 patients with essential hypertension. All received two bolus i.v. injections in the mean dose range of (0.78--3.36 micrograms kg-1) and one single oral dose (mean dose 1.7--2.3 micrograms kg-1) on separate occasions. The kinetics were also studied in some of these patients after multiple therapeutic oral dose (mean dose 1.1 or 1.9 micrograms kg-1) twice daily during a dosage interval after 6--12 months monotherapy with clonidine. The multiple oral dosage was based on the therapeutic response. 2 With increasing i.v. doses the rate constants (alpha, beta) decreased and the plasma clearance was reduced by 74%(9.94--2.61 ml min-1 kg-1) indicating dose-dependent kinetics. The volume of distribution (Vd beta) did not change with dose in contrast to the volume of the plasma compartment (Vc) which was increased at the highest doses. 3 The single oral dose kinetics agreed with the i.v. kinetics at comparable dose. The bioavailability was 90%. 4 During multiple oral dosing the elimination rate constants decreased compared to the single dose. The plasma clearance increased (7.18 ml min-1 kg-1) compared to the corresponding single dose (4.17 ml min-1 kg-1). The latter change was probably caused by the decrease in bioavailability to about 65%. 5 The pharmacodynamic properties of the drug could explain the changes in pharmacokinetics with increased dose and during multiple doses.

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 4.68 +/- 0.191.min-1. The blood flow and respiratory exchange ratio correlated positively to the percentage of slow-twitch fibres in the vastus muscles. No correlation was found between the muscle fibre composition and either oxygen uptake heart rate or mechanical efficiency. The results with a dependence of muscle blood flow and carbon dioxide release to muscle fibre composition support the view that the arrangement of the vascular bed and blood supply differ between fast-twitch and slow-twitch muscle fibres in humans.

Recording of multi-unit sympathetic activity were made from muscle branches of the peroneal nerve during i.v. bolus injection of 100 to 275 micrograms clonidine in seven hypertensive patients. Blood pressure was reduced in all patients, but sympathetic activity and heart rate could either increase or decrease. When plasma levels of clonidine were low, sympathetic activity tended to increase, and when plasma levels were high, activity tended to decrease. Irrespective of whether mean level of sympathetic activity increased or decreased with the fall in blood pressure level, transient fluctuations of blood pressure continued to cause dynamic baroreflex modulation of the sympathetic outflow. It is suggested that the drug influences sympathetic outflow by a combination of central and peripheral effects.

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. The reaction pattern was similar in both groups. Except for systolic and diastolic blood pressures tonic cardiovascular and electrodermal activity of the HT group was not different from that of the NT group. The same pattern, although less clear cut, was observed when reactivity was studied. According to analyses based on pressure levels both tasks raised the systolic blood pressure of the HT group, whereas only the rejection task raised systolic blood pressure in the NT group. In contrast, an analyses based on blood pressure changes from base to task indicated that both groups increased systolic blood pressure to both tasks. Since virtually no other differences in reactivity were found, this study offers weak support for the notion that subjects having essential arterial hypertension are pressor hyper-reactors.

Arterial blood pressure (BP), skin conductance level (SCL) and spontaneous fluctuations in skin conductance (SFs) were monitored in 14 subjects with essential hypertension (HT), and 14 matched normotensive (NT) controls during a letter identification task (L) and mental arithmetic (MA). During both tasks, the groups displayed different response patterns such that SFs and BP tended to be negatively correlated in the HT group but were positively correlated in the NT group. No correlation between BT and SCL was obtained in any group during either task. SFs and SCL were positively correlated in the NT group during both tasks whereas no correlation was found in the HT group. The results are consistent with the hypothesis that an increased BP is associated with the rejection of the environment.