Feb 20, 1981 - pressure and prazosin plasma concentration correlated (P < 0.01) during the 0-elimination phase in all patients. In only five of eight patients, ...
Prazosin dynamics in hypertension: Relationship to
plasma concentration The antihypertensive effects of prazosin in relation to its kinetics were studied after single doses
(intravenous and oral, 0.5 mg) and during increasing multiple doses (0.5 to 5 mg three times a day). There was a MI in systolic and diastolic blood pressures of 10% to 14%, which was greater in the standing than in the sitting position. Prazosin plasma concentrations correlated with dose (P < 0.001). After intravenous prazosin the fall in systolic and diastolic blood pressure and prazosin plasma concentration correlated (P < 0.01) during the 0-elimination phase in all patients. In only five of eight patients, however, did mean plasma concentration and antihypertensive effect during continuous treatment with different doses correlate. The maximal ,fall in systolic blood pressure correlated (P < 0.01) with that after the .first oral steady-state dose (0.5 mg three times daily), which indicates limited possibility of early identification of prazosin responders. There were no signs of overshoot of blood pressure when prazosin was withdrawn for a week. On rechallenge with a single oral dose of 2.5 mg prazosin there were no signs of enhanced hypotensive effect.
Peter Seideman, M.D., Anders Grahnen, M.Pharm., Kjell Haglund, M.D., BjOrn Lindstram, Ph.D., and Christer von Bahr, M.D. Huddinge, Stockholm, and Uppsala, Sweden Departments of Internal Medicine and Clinical Pharmacology, Huddinge University Hospital, Huddinge, Karolinska Institute, Stockholm, and Department of Drugs, National Board of Health and Welfare, Uppsala
Prazosin is supposed to reduce peripheral vascular resistance by blocking vascular aradrenergic receptors.4' Unlike hydralazine, prazosin causes only minor reflex tachycardia16' 19' 24; it is effective in moderate and severe hypertension in 23 and betacombination with diuretics4'
Supported by grants from The Loo and Hans Osterman fund, the Swedish National Association against Chest and Heart Diseases, and the Swedish Medical Research Council (04X-03902). Received for publication Feb. 20, 1981. Accepted for publication July 20, 1981. Reprint requests to: Dr. Peter Seideman, Department of Internal Medicine, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
0009-9236/81/100447+08$00.80/0
receptor blocking drugs:4' 18 In some clinical situations it can be used alone,4' 7' 29' 28 although the effectiveness of this treatment has been disputed.25' 28 Only few studies have focused on prazosin dynamics and kinetics,2' 11, 15' 29 and none have been performed (in hypertensive patients) comparing single intravenous and oral doses, different doses at steady state, and withdrawal and rechallenge of prazosin. Our aim was to relate dose and plasma concentration to antihypertensive effects and investigate the predictability of the antihypertensive response from the first or one of the early prazosin doses. We wanted to uncover dose-dependent kinetics
0 1981 The C. V. Mosby Co.
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Clin. Pharmacol. Ther. October 1981
Seideman et al.
Table I. Patient characteristics
ECG
Chest x-ray film
98 74 70
15 3
83 110 65 85
0
normal LVH normal normal LVH normal normal normal
normal normal normal normal normal normal normal normal
Weight (kg)
2 3
37 54 54
4
51
5
35 28 42 37
Patient No.
Sex
1
6 7 8
Duration* of hypertension (yr)
Age (yr)
1
10 1
0
76
1
LVH = Left ventricular hypertrophy. *From records or history.
Table II. Dose, blood pressure, and pulse rate (AUC) during placebo and prazosin therapy Pulse rate
Patient No.
Daily dose of prazosin (mg)
Sitting
Placebo
Prazosin
Placebo
57 75 72 69 70 85 72 87
58 79 74 75 67 84 79 90
74
76
3
12 15
4
6
5
3
47 74 70 69 60
6 7
3
71
6
8
6
74 75
6.8
68
1
2
Mean
3
Stan ding
P
or abnormal blood pressure increase after prazosin withdrawal. Material and methods
Patients. Patient characteristics are presented in Table I. The study included eight patients
with essential hypertension (World Health Organization Classification I to II) who had diastolic blood pressure above 105 mm Hg as a mean of three ambulant measurements (after 10 min rest in the supine position) by the same investigator. Secondary hypertension was excluded by routine procedures. None had received antihypertensive therapy during the last year and only a few had a history of a prior short antihypertensive therapy. Ages ranged from 28 to 54 yr. None of the subjects used alcohol excessively and they were instructed to refrain from using it during the study. Three patients
< 0.05
Prazosin 76 81
77 82
80 103
79 103
p
