Clinical pharmacology and pharmacokinetics of clonidine

Dollery, C. T.; Davies, Donald S.; Draffan, G. H.; Dargie, H. J.; Dean, Caron; Reid, John L.; Clare, R. A.; Murray, Stephen A.

doi:10.1002/cpt197619111

Cited by 265 publications

(90 citation statements)

References 5 publications

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“…The half-life of the /3-phase was increased two-fold to 12.8 + 2 h after the highest dose of 3.36 ug kg-' compared to that after the lowest dose 6.2 + 2.3 h. The total plasma clearance similarly decreased by -74% from 9.94 to 2.61 ml min-' kg-' ( Table 2). The AUC increased in a linear manner with dose except for the highest dose ( half-life was also in agreement with that previously found by us (Frisk-Holmberg et al, 1978) and others (Wing et al, 1977;Dollery et al, 1979) studying hypertensive patients. The bioavailability after the single oral doses was high, -90%.…”

Section: Analysis Ofdatasupporting

confidence: 92%

“…Dollery and coworkers have studied the kinetics after single oral doses in a few normotensive and hypertensive patients and also investigated the kinetics after multiple dose administration (Wing et al, 1977;Dollery et al, 1979). The authors claimed that the kinetics after a single dose did not change after 1 week of treatment and were similar in these subjects.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Frisk-Holmberg¹,

Paalzow²,

Edlund³

1981

Brit J Clinical Pharma

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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.

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Section: Analysis Ofdatasupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

Frisk-Holmberg¹,

Paalzow²,

Edlund³

1981

Brit J Clinical Pharma

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“…The a2-adrenoceptor blocking drug, clonidine, is known to produce sedation in man following acute administration (Dollery et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

“…Studies in man 1978) and man (Dollery et al, 1976). In addition, indicate that azepexole significantly reduces clonidine facilitates the vagally mediated baro-systolic and diastolic blood pressure in the supine receptor reflex in animals (Kobinger & Walland, and standing position without effect on heart 1971,1972) and in man (Sleight & West, 1975;rate; associated with these cardiovascular effects Guthrie & Kotchen, 1983).…”

Section: Introductionmentioning

confidence: 97%

Effects of azepexole and clonidine on baroreceptor mediated reflex bradycardia and physiological tremor in man.

Harron¹,

Riddell²,

Shanks³

1985

Brit J Clinical Pharma

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1 The effects of oral administration of axepexole 10 mg, clonidine 300 ,ug and placebo on baroreceptor mediated reflex bradycardia and physiological tremor were investigated in six healthy volunteers. 2 Both azepexole and clonidine reduced (P < 0.05) systolic (120.5 ± 2.5 to 105.0 + 3.3 mm Hg; 115.8 + 2.6 to 104.7 + 2.8 mm Hg respectively) and diastolic (52.5 + 2.6 to 47.2 + 1.4 mmHg; 53.7 + 1.6 to 49.0 ± 1.5 mmHg respectively) pressure when compared to placebo and to pre-treatment values. This reduction in pressure was not accompanied by a change in heart rate. 3 Both azepexole and clonidine enhanced (P < 0.05) baroreflex sensitivity to increases in systolic arterial pressure with phenylephrine. 4 Clonidine facilitated (P < 0.05) baroreflex sensitivity during the strain phase of the Valsalva manoeuvre, whereas azepexole reduced it (P < 0.05). 5 Neither clonidine nor azepexole altered finger tremor when compared to placebo or pre-treatment values. 6 Azepexole produced (P < 0.05) sedation compared to placebo but not when compared to pre-treatment values. Clonidine caused significant increases in sedation when compared to both placebo and to pre-treatment values. 7 The differences between azepexole and clonidine may be due to the greater specificity of azepexole for the a2-adrenoceptor than clonidine.

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“…The method of measurement is a variation of that reported by Dollery, Davies, Draffan, Dargie, Bean, Reid, Clare & Murray (1976), in which pre-weighed cotton wool dental rolls were placed in the mouth for a fixed period of time, then removed and re-weighed. We have adopted this method for the rabbit.…”

Section: Salivationmentioning

confidence: 99%

Comparison of the Actions of Centrally and Peripherally Administered Clonidine and Guanfacine in the Rabbit: Investigation of the Differences

Barber

Reid

1982

British J Pharmacology

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1Guanfacine was administered intravenously to rabbits and produced a dose-dependent lowering of blood pressure.2 Clonidine and guanfacine, administered to rabbits intravenously (30 Ag/kg and 300 Ag/kg respectively) and intracisternally (3 jLg/kg and 12 gLg/kg respectively) caused a similar degree of hypotension, apparently of central origin. 3 Saliva flow in vivo was estimated. Clonidine (30 jAg/kg, i.v.) caused a significant decrease in salivation (P<0.05) for the first 50min after injection. Guanfacine caused a significant fall (P< 0.05) only at 50 and 180 min after injection. 4 Apparent partition coefficients for an octanol/buffer system at pH 7.4 for clonidine and guanfacine were 5.4 and 21.2 respectively. 5Measurement of guanfacine levels concurrently in both plasma and brain showed that guanfacine had higher brain than plasma levels and that the brain levels were fairly constant over the 3 h measured. Brain:plasma ratios were 2.1:1, 5.3: 1 and 13.6: 1 after 15,90 and 180 min respectively. 6 These results suggest that the long duration of action of guanfacine is due to its persistence at its central site of action.

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Clinical pharmacology and pharmacokinetics of clonidine

Cited by 265 publications

References 5 publications

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

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

Effects of azepexole and clonidine on baroreceptor mediated reflex bradycardia and physiological tremor in man.

Comparison of the Actions of Centrally and Peripherally Administered Clonidine and Guanfacine in the Rabbit: Investigation of the Differences

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