摘要:

Clinical Pharmacology and Therapeutics(1981)29,291–294; doi:10.1038/clpt.1981.

ISSN:0009-9236    

DOI:10.1038/clpt.1981.38

年代:1981

数据来源: WILEY

摘要:

Beta adrenoceptor blockers differ mainly in their plasma elimination half‐lifes (t½s). It has been assumed that drugs with longer t½s will have a longer duration of effect on exercise tachycardia. Several factors may influence the duration of action of beta blockers; we have investigated the contribution of plasma elimination t½ and dose by comparing the effects on an exercise tachycardia in healthy subjects of placebo, 25, 50, 100, and 200 mg of atenolol and of sotalol, and 50, 100, 200, and 400 mg metoprolol. Subjects exercized before and at 2, 3, 6, 8, 24, 33, and 48 hr after oral doses of each drug. Plasma samples for measurement of drug concentration were drawn before each exercise period. Twenty‐four hours after 50, 100, and 200 mg atenolol and 50, 100, 200, and 400 mg sotalol there were reductions in an exercise tachycardia; at this time reductions were greater after the larger doses. The plasma elimination t½s of atenolol were between 7.2 ± 1.2 and 9.1 ± 1.6 hr and for sotalol were 9.2 ± 0.7 and 10.1 ± 1.0 hr. Although 50, 100, and 200 mg metoprolol induced the same reductions in an exercise tachycardia 2 hr after drug as 25, 50, and 100 mg atenolol and 50, 100, and 200 mg sotalol, these doses were without effect at 24 hr. Metoprolol 400 mg reduced exercise tachycardia at 24 hr but the effect was less than that of the three largest doses of atenolol and sotalol. The plasma elimination t½ for metoprolol was between 3.6 ± 0.6 and 5.0 ± 1.8 hr. These results show that duration of cardiac beta blocking activity of atenolol, sotalol, and metoprolol is determined by the elimination t½ and dose.Clinical Pharmacology and Therapeutics(1981)29,295–302; doi:10

ISSN:0009-9236    

DOI:10.1038/clpt.1981.39

年代:1981

数据来源: WILEY

摘要:

Initiation of prazosin therapy may be complicated by the first‐dose response of acute postural hypotension and tachycardia. The effects of β‐blocker on the responses to oral prazosin were studied in eight normotensive men. After 1 mg oral prazosin there was a marked postural fall in blood pressure to a lowest mean standing systolic pressure of 88 ± 7 mm Hg (x̄ ± SD), associated with a tachycardia of 117 ± 13 bpm, and an increase in mean plasma norepinephrine concentration to 9.6 ± 7.9 nmole/l. There was a linear relationship (r = 0.93) between plasma prazosin concentration and hypotensive effect. Concurrent propranolol 80 mg or primidolol 100 mg (a cardioselective β‐blocker) increased the severity and duration of the postural hypotensive response, with lowest mean systolic blood pressure (BP) of 79 ± 7 and 75 ± 9 mm Hg. There was no effect on the orthostatic release of norepinephrine but there was attenuation of the postural tachycardia. Concurrent β‐adrenergie blocking therapy, selective or nonselective, intensifies the immediate postural hypotensive response to the initial oral dose of prazosin.Clinical Pharmacology and Therapeutics(1981)29,303–309; doi:

ISSN:0009-9236    

DOI:10.1038/clpt.1981.40

年代:1981

数据来源: WILEY

摘要:

Studies of renal hemodynamics were carried out in 84 patients with essential hypertension during long‐term antihypertensive therapy with a number of drugs. Renal perfusion was maintained or enhanced despite a fall in mean arterial pressure during therapy with hydrochlorothiazide, furosemide, clonidine, prazosin, and the combination of guanabenz and hydrochlorothiazide. Renal perfusion deteriorated during long‐term treatment with propranolol. Renal hemodynamics may be enhanced, maintained, or adversely influenced depending on the choice of antihypertensive agent.Clinical Pharmacology and Therapeutics(1981)29,310–317; doi:10.1038/clpt.1

ISSN:0009-9236    

DOI:10.1038/clpt.1981.41

年代:1981

数据来源: WILEY

摘要:

The effects of large oral doses of ascorbic acid on renal clearance and excretion of uric acid were studied in nongouty subjects because ascorbic acid has been reported to increase renal uric acid clearance. Our results indicate that 4 or 12 gm ascorbic acid taken in divided doses had no effect on serum uric acid concentration or uric acid excretion and clearance by the kidney. Reasons for these results, which differ from previous reports, are discussed. We quantitated the magnitude of the interference of ascorbic acid in the measurement of uric acid by the nonspecific methods frequently used, since falsely elevated urine uric acid could lead to misinterpretation of screening tests.Clinical Pharmacology and Therapeutics(1981)29,318–321; doi:10.1038/clpt.1981.

ISSN:0009-9236    

DOI:10.1038/clpt.1981.42

年代:1981

数据来源: WILEY

摘要:

Disopyramide hemodialysis and kinetics after 200 mg orally in six patients receiving long‐term hemodialysis were examined. Mean volume of distribution (area) was 66.5 ± 13 1. Mean times of the peak serum concentration and mean peak serum concentration were 2.3 ± 0.9 hr and 3.1 ± 0.9 µg/ml. Mean absorption half‐life (t½) was 21.6 ± 12.5 min. Mean disopyramide elimination t½ during dialysis was 16.8 ± 11.9 hr, not significantly different from mean elimination t½ without dialysis of 16.1 ± 5.2 hr. End‐dialysis bath concentrations of disopyramide showed that not more than 2.4% of the dose was dialyzed during a 2‐hr dialysis period. Our data indicate that at therapeutic concentrations disopyramide was not appreciably dialyzed.Clinical Pharmacology and Therapeutics(1981)29,322–326; doi:

ISSN:0009-9236    

DOI:10.1038/clpt.1981.43

年代:1981

数据来源: WILEY

摘要:

Beta adrenoceptor sensitivity may be altered in thyrotoxicosis and myxedema. We therefore studied β‐adrenoceptor responses of peripheral blood lymphocytes to stimulation with 10−9to 10−6M(–)‐isoproterenol from patients before and after treatment of myxedema and thyrotoxicosis as well as in patients without thyroid disease. There were six patients in each group. Lymphocyte basal cyclic adenosine monophosphate (cAMP) concentrations were higher in untreated thyrotoxicosis (4.94 ± 0.46 pmole/106cells) than in controls (3.47 ± 0.42 pmole/106cells, p<0.05) and in untreated myxedema (3.11 ± 0.50 pmole/106cells, p<0.025). The full isoproterenol dose‐response curves were similar in all groups. Calculated maximum velocity (Vmax) showed an approximate increase in cAMP of 14.5 pmole/106cells. Isoproterenol concentrations at half‐maximum velocity (EC30) were approximately 10−8M. It is concluded that lymphocyte β2‐adrenoceptor responses are not altered in hypothyroidism and hyperthyroidism.Clinical Pharmacology and Therapeutics(1981)29,327–331;

ISSN:0009-9236    

DOI:10.1038/clpt.1981.44

年代:1981

数据来源: WILEY

摘要:

To evaluate the interaction of disulfiram with the separated enantiomorphs of racemic warfarin, seven normal subjects received single doses of R‐warfarin (1.5 mg/kg body weight) and S‐warfarin (0.75 mg/kg body weight) with and without a daily dose of disulfiram 250 mg, beginning 3 days before the warfarin dose and continuing for the duration of the hypoprothrombinemia. Disulfiram augmented the S‐warfarin hypoprothrombinemia (p0.40). Disulfiram augments the hypoprothrombinemia of racemic warfarin stereoselectively by interacting primarily with S‐warfarin. As disulfiram did not change the plasma concentrations of either enantiomorph, it may augment the anticoagulant effect of racemic warfarin by directly affecting the hepatic mechanism responsible for the hypoprothrombinemia.Clinical Pharmacology and Therapeutics(1981)29,332–336; doi:10.1

ISSN:0009-9236    

DOI:10.1038/clpt.1981.45

年代:1981

数据来源: WILEY

摘要:

The effect of dose on acetylator phenotype distribution of hydralazine has been determined. The acetylated metabolites methyltriazolophthalazine (MTP) and 3‐hydroxymethyltriazolophthalazine (3‐OHMTP) and acid‐labile hydralazine (HP) were determined in the 0‐ to 24‐hr urine of patients receiving various doses. The difference between the mean value for the ratio 3‐OHMTP: HP in the rapid and slow acetylators varied with dose, the greatest difference being after a 200‐mg (100 mg twice daily) dose. The distribution of the ratio became less clearly bimodal at lower doses, with overlap between phenotypes occurring at doses of 100 mg (50 mg twice daily) or less. The most effective dose for discriminating between acetylator phenotypes was found to be 200 mg (100 mg twice daily).Clinical Pharmacology and Therapeutics(1981)29,337–343; doi:10.1

ISSN:0009-9236    

DOI:10.1038/clpt.1981.46

年代:1981

数据来源: WILEY

摘要:

Racemic indacrinone is a high‐ceiling, relatively long‐acting diuretic. Both enantiomers have uricosuric activity, but the diuretic activity resides predominantly in the (−) enantiomer. Usual therapeutic doses of racemic indacrinone have only transient uricosuric activity, so that, as with other diuretics, hyperuricemia occurs. Sixty‐five healthy men participated in a multicenter, double‐blind, randomized, balanced, incomplete‐block study comparing the effects on plasma urate and urate clearance of indacrinone (—) enantiomer 10 mg given concomitantly with 0, 10, 20, 40, and 80 mg (+) enantiomer (10/0, 10/10, 10/20, 10/40, 10/80), as single daily doses for 7 days. Hydrochlorothiazide (HCTZ) 50 mg daily and ticrynafen (T) 250 mg daily were controls. Each subject received two of the seven treatments, so that there were 18 subjects per treatment. On days 7 to 8, morning (mean of 0‐hr values on days 7 and 8), HCTZ, 10/0, 10/10, and 10/20 elevated plasma urate by 8% to 16%, 10/40 was approximately isouricemic, and 10/80 and T lowered plasma urate by 13% and 41%. There were corresponding changes in urate clearance.Clinical Pharmacology and Therapeutics(1981)29,344–350; doi:10

ISSN:0009-9236    

DOI:10.1038/clpt.1981.47

年代:1981

数据来源: WILEY