摘要:

Clinical Pharmacology and Therapeutics(1988)43,1–2; doi:10.1038/clpt.1988

ISSN:0009-9236    

DOI:10.1038/clpt.1988.1

年代:1988

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1988)43,3–3; doi:10.1038/clpt.1988

ISSN:0009-9236    

DOI:10.1038/clpt.1988.3

年代:1988

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1988)43,4–5; doi:10.1038/clpt.1988

ISSN:0009-9236    

DOI:10.1038/clpt.1988.4

年代:1988

数据来源: WILEY

摘要:

The effects of nitrendipine (10 mg, during acute clearance experiments) given both acutely and after 2 weeks of administration were examined in normal and hypertensive subjects. At the initiation of therapy, nitrendipine caused an increase in glomerular filtration rate and effective renal plasma flow in the hypertensive, but not in the normal, group. Percentage excretion rates of sodium (%ENa) and phosphate (%EPi) and free water clearance (CW) increased in both groups at the initiation of therapy. After 2 weeks of nitrendipine therapy repeat acute clearance studies showed that the drug no longer increased glomerular filtration rate or effective renal plasma flow in hypertensive subjects, the increases in %ENa and CW persisted in normal subjects and trended upward in hypertensive subjects, and the increase in %EPi persisted in both normal and hypertensive individuals. We conclude that nitrendipine is not sodium retentive after chronic therapy and the acute increase in %ENa, %EPi, and CW after its initial administration suggests a proximal tubular effect.Clinical Pharmacology and Therapeutics(1988)43,6–15; doi:10.1038/clpt.1988

ISSN:0009-9236    

DOI:10.1038/clpt.1988.5

年代:1988

数据来源: WILEY

摘要:

The pharmacokinetics and some hemodynamic effects of three dihydropyridine (DHP) calcium channel blockers were studied in healthy subjects. In a randomized order, each subject was given 24 μg/kg nifedipine, 40 μg/kg nitrendipine, or 10 μg/kg nisoldipine intravenously. The three DHPs differed as to their total clearance and volume of distribution (nifedipine

ISSN:0009-9236    

DOI:10.1038/clpt.1988.6

年代:1988

数据来源: WILEY

摘要:

The effects of tobacco and oral contraceptive (OC) use (Ovral) on the pharmacokinetics of levonorgestrel (0.25 mg) and ethinyl estradiol (50 μg) were examined. Young women (n = 27) were grouped as follows: I: non‐OC users/nonsmokers; II: OC users/nonsmokers; III: non‐OC users/smokers; and IV: OC users/smokers. The apparent clearance of levonorgestrel in group I was 80.9 ± 15.6 ml/hr/kg and the half‐life was 19.3 hours. A significant decrease in levonorgestrel clearance was seen in the chronic OC users (groups II and IV). The apparent oral clearance of ethinyl estradiol was 1002 ± 398 ml/hr/kg in group I and the half‐life averaged7.7hours. Groups II and III showed decreased (not significant) clearances of ethinyl estradiol. Tobacco use had no effect on steroid pharmacokinetics in the non‐OC users. Although chronic OC use did not affect ethinyl estradiol clearance, a joint effect of tobacco/OC use on enhancing clearance of ethinyl estradiol appeared to occur. A linear relationship was found between 24‐hour trough serum concentrations and AUC values of both steroids that may facilitate population monitoring studies of OC exposure.Clinical Pharmacology and Therapeutics(1988)43,23–31; doi:10

ISSN:0009-9236    

DOI:10.1038/clpt.1988.7

年代:1988

数据来源: WILEY

摘要:

Responses to intravenous clonidine, a possible central noradrenergic probe, were examined in patients with depression before and after treatment with clorgiline, a selective monoamine oxidase type A inhibitor. Pulse rate, mean arterial blood pressure, plasma norepinephrine, 3‐methoxy‐4‐hydroxyphenylglycol, and growth hormone were measured. Clorgiline treatment (2.5 to 10 mg/day) produced a variable reduction in the hypotensive response to clonidine but did not influence heart rate or plasma norepinephrine responses. Clorgiline markedly reduced the urinary output of norepinephrine and metabolites, indicating a reduced turnover of norepinephrine. None of the measured parameters corresponded with clinical effect. These data suggest that any clorgiline‐induced alterations in α2‐receptor function as measured by responses to clonidine are modest and highly variable. Furthermore, since the variable and inconsistent changes in α2‐receptor function are dissociated from the massive changes in norepinephrine metabolism, regulation of presynaptic α2‐receptors appears unlikely to mediate the effects of clorgiline in patients with depression.Clinical Pharmacology and Therapeutics(1988)43,32–38; doi:

ISSN:0009-9236    

DOI:10.1038/clpt.1988.8

年代:1988

数据来源: WILEY

摘要:

The pharmacokinetic and pharmacodynamic effects of nisoldipine, a 1,4‐dihydropyridine calcium entry blocker, and the lipophilic β‐adrenoceptor blocker propranolol were assessed alone and in combination in 12 healthy men. Oral nisoldipine, 20 mg, or placebo was followed 1 hour later by propranolol, 40 mg, or placebo using a randomized, crossover, double‐blind design. Nisoldipine significantly increased the AUC (+ 43%) and peak plasma drug concentration (Cmax) (+ 68%) of propranolol resulting in a higher degree of β‐adrenoceptor blockade (as assessed by isoproterenol). Conversely, nisoldipine's AUC (+ 30%) and Cmax(+ 57%) were increased with concomitant administration of propranolol. Nisoldipine did not affect blood pressure but caused significant decreases in total peripheral resistance (TPR) and increases in plasma catecholamines and cardiac index. Forearm vascular resistance and blood flow changed more markedly than did TPR and cardiac index. In contrast, propranolol had little effect on forearm hemodynamics despite significant decreases in cardiac index and increases in TPR. The data are compatible with changes in hepatic blood flow, accounting for the pharmacokinetic interaction of nisoldipine and propranolol. Different vascular beds appear to contribute to the effects of nisoldipine vs. propranolol on peripheral resistance.Clinical Pharmacology and Therapeutics(1988)43,39–48; doi:10.1038

ISSN:0009-9236    

DOI:10.1038/clpt.1988.9

年代:1988

数据来源: WILEY

摘要:

To assess the vascular involvement of renin‐angiotensin system inhibition in human hypertension, acute effects of intravenous enalaprilat on brachial artery diameter, blood flow, and blood velocity were investigated in hypertensive patients by pulsed Doppler technique and compared with effects of saline vehicle. Compared with saline vehicle, enalaprilat reduced blood pressure (P<0.001) and increased brachial arterial diameter (P<0.01) and brachial blood flow (P<0.01). Enalaprilat effect on arterial pulse pressure was dependent on preinjection pulse pressure (r = −0.76; P<0.001), but its effect on mean blood pressure was not dependent on preinjection mean blood pressure. On the other hand, enalaprilat effect on arterial blood flow was negatively correlated with preinjection blood pressure (r = − 0.64; P<0.02). The findings point to different responses of large and small arteries to intravenous enalaprilat.Clinical Pharmacology and Therapeutics(1988)43,49–54; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1988.10

年代:1988

数据来源: WILEY

摘要:

We determined the AUC of cyclosporine (24 hours) nonspecifically by RIA and specifically by HPLC after an oral and an intravenous dose of cyclosporine in 58 patients undergoing renal transplantation. The RIA/HPLC concentration ratio of cyclosporine changed continuously during the first 12 hours after administration. The ratio was higher after oral than after intravenous administration and varied from patient to patient. The predictive value of trough levels for the corresponding AUCs was better when trough levels were assessed 24 than 12 hours after administration. Trough levels assessed by RIA poorly predicted AUCs measured specifically by HPLC. Therefore if, in the future, therapeutic cyclosporine monitoring has to be improved, trough levels should be assessed 24 hours after the last dose by means of a specific HPLC method.Clinical Pharmacology and Therapeutics(1988)43,55–62; doi:10.1038/clpt.1988.

ISSN:0009-9236    

DOI:10.1038/clpt.1988.11

年代:1988

数据来源: WILEY