ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03812.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03813.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03814.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03815.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The disposition of a single 20‐mg oral dose of pravastatin was assessed in subjects with various degrees of renal function. Sixteen subjects (13 males, 3 females) with creatinine clearance values ranging from 15 to 112 mL/min/1.73 m2completed the study. Area under the serum concentration‐time curve, maximum serum concentration, time to maximum serum concentration, terminal serum elimination half‐life, apparent clearance, and apparent volume of distribution for pravastatin were not affected by renal impairment, whereas the renal clearance of pravastatin decreased as creatinine clearance decreased (r2= 0.697, P<.001). The area under the serum concentration‐time curve and time to maximum serum concentration of SQ 31,945 (a hepatic metabolite) increased in patients with renal impairment, whereas the terminal elimination rate constant and renal clearance of SQ 31,945 significantly decreased as a function of creatinine clearance. The renal clearance of another metabolite (SQ 31,906) also significantly declined with decreasing renal function. This single‐dose study demonstrates that pravastatin pharmacokinetics were not affected in patients with renal impairment, probably because of its dual route of el

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03816.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

In a double blind, randomized trial the effects of aspirin (1, 5, and 15 mg/kg) were compared with the changes in platelet aggregation at 6 and 24 hours after dosage. It is found that there is a negative correlation between aspirin hydrolysis velocity in blood and capability of aspirin to decrease platelet aggregation with ADP and collagen in patients with atherosclerosis. Relationship between these parameters depends on aspirin dosage. The correlation was more marked for low doses of aspirin. It is suggested that the effect of aspirin in low dosage on platelet aggregation might be ineffective in many patients without control of aspirin hydrolysis velocity in blood.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03817.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Twelve healthy male volunteers received single market‐image 40‐mg oral doses of lovastatin and simvastatin (both lactone prodrugs), or pravastatin (α β‐hydroxyacid) at 1 week intervals in a three‐way crossover study to quantify HMG‐CoA reductase inhibitors in plasma. Multiple plasma samples were collected up to 24 hours after the dose and assayed for active and total HMG‐CoA reductase inhibitors. After equal oral doses, higher plasma concentrations of HMG‐CoA reductase inhibitory activity after pravastatin than after either lovastatin of simvastatin (2–3 fold greater area under the concentration‐time curve) suggest a greater potential availability of pravastatin‐related inhibitory activity

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03818.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Advances in critical care medicine have increased survival for victims of myocardial infarction and other acute cardiac events so that increasingly patients are receiving long‐term, labor‐intensive, and costly medical care. Innovations in drug delivery systems and skyrocketing health care costs have fostered the growth of home health care which has blossomed into a $2.8 billion industry. There is evidence that outpatient dobutamine therapy produces definite physical and possibly psychological improvements of variable degree and duration. Hemodynamic improvements are generally associated with improvement in functional class, and the financial savings are recognizably substantial. However, three major problems confront therapies with beta‐adrenergic agonists: tendency for tolerance, ventricular arrhythmias, and increased myocardial oxygen consumption. There is a dire need for establishment of exclusionary patient criteria and for risk stratification, as well as for development of a portable radionuclide nonimaging monitor. Given the current fund of knowledge, outpatient dobutamine therapy should be undertaken cautiously after meticulous patient selection reflecting an awareness of the tremendous complexities and inherent risks. The therapeutic implications are dependent on the nature of the underlying cardiomyopathy and the fact that beta‐adrenergic receptor desensitization is unlikely to be overcome by progressive dosage increases. Therapy is initiated with the understanding that treatment will remain blindly empirical and conjectural in the absence of a continuous physiologic monitor and an expanded comprehension of the molecular pathophysiology of the failing ve

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03819.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Acebutolol (AC) is a chiral β‐blocker that is metabolized to an equipotent chiral metabolite, diacetolol (DC). A stereoselective disposition of AC and DC enantiomers has recently been reported in young healthy subjects. As many physiologic properties affecting drug disposition are progressively altered with increasing age, the effect of aging on the pharmacokinetics of AC and DC enantiomers were investigated in nine subjects ranging from 60 to 75 years after administration of an oral 200‐mg dose of racemic AC. Increasing age resulted in a significant prolongation of the elimination t1/2s of R‐ (r=0.913) and S‐DC (r=0.811). Also, the S:R ratios of AC urinary excretion (ΣXu) of enantiomers was significantly correlated with age (r=0.677). Contribution of declining renal junction to age‐associated pharmacokinetics changes was subsequently examined. Renal clearance and cumulative urinary excretion of both AC and DC enantiomers were positively correlated with creatinine clearance. In addition, declining creatinine clearance was associated with a subsequent decline in the enantiomer S:R ratio of AC in plasma (AUC S:R, r=0.807) and urine (ΣXu S;R r=0.807). Similarly, a progressive decline in the S:R ratio of DC collected in urine was evident (r=0.689). Age‐related changes in the enantiomers ratios may suggest that an active stereoselective pathway such as renal tubular secretion or nonrenal excretion may be affected

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03820.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Nine healthy subjects received 0.2 mg of beta‐methyldigoxin (β‐MD) orally in the fasting state, 30 minutes after and before a standard breakfast. The time‐to‐peak serum glycoside concentration was delayed and the peak concentration was lower in the postprandial state compared with the other regimens (P<.01). The absorption rate constant was significantly reduced when β‐MD was given after a meal (1.55 ± 1.75 hr−1) than before a meal (5.54 ± 2.16 hr−1) and in the fasting state (5.22 ± 3.06 hr−1)(P<.01). Although the area under the serum glycoside concentration‐time curve and the cumulative urinary excretion (CUE) of β‐MD, digoxin, and total drug (β‐MD plus digoxin) was not significantly different between three regimens, the CUE∞tended to be smaller in the postprandial state compared with before a meal. The results indicate that the timing of drug administration in relation to a meal is an important factor leading to the fluctuations of serum glycoside concentration after oral β‐MD, which mig

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03821.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY