ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02794.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02795.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02796.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Nifedipine is a calcium‐channel antagonist with effective antihypertensive activity and has been suggested for the treatment of high blood pressure as an alternative to vasodilators. The aim of this study was to define the acute effect of nifedipine and in particular the dose‐effect relationship, effects on veins, influence on adrenergic reflexes, and effectiveness on hypertension according to severity and etiologic type. The effects of nifedipine on blood pressure, heart rate, forearm blood flow, peripheral vascular resistance, orthostatic and cold reflexes, and venous tone were examined in 45 patients with hypertension of different etiologies (essential, renovascular, and renal parenchymal) and different World Health Organization grades. The antihypertensive effect was dose dependent, but a dose of 20 mg has nearly maximal activity with acceptable side effects. The drug acts by lowering peripheral vascular resistance, and this lowering is directly related to baseline values; therefore, the antihypertensive effect increases with severity of the hypertension. Nifedipine had the same effect in all three etiologic groups of hypertension studied. The drug seems to increase venous tone, since it caused venoconstriction when locally injected in hand veins. Nifedipine did not alter adrenergic reflexes induced by both cold application and standing and was well tolerated. In conclusion, the calcium antagonist nifedipine for its characteristics of action, at least in acute administration, seems to be a useful alternative in the treatment of various forms of hypertens

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02797.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Bioequivalence comparisons between erythromycin ethylsuccinate and an enteric‐coated erythromycin base pellet product were made following multiple‐dose, oral administration. Twenty‐four volunteers participated in a ten‐dose protocol (one dosage unit every six hours) using a complete crossover design. Plasma samples were assayed using a microbiological method specific for erythromycin base in the presence of the ester. Without correcting for the differences in doses administered, the amount of active erythromycin base absorbed from the enteric‐coated pellet (250 mg base) was five to seven times that absorbed from the erythromycin ethylsuccinate product (400 mg base equivalent) at steady state. Erythromycin ethylsuccinate is not bioequivalent to an enteric‐coated erythromycin base pellet product The lower bioavailability of the ethylsuccinate may be due to instability in the acidic medium of

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02798.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Six patients were given tracer doses of13C15N2‐phenytoin (PHT) before and four and 12 weeks after beginning monotherapy. The following significant (P<.05) changes occurred during monotherapy: (1) Apparent (from tracer doses) PHT total clearance by linear method decreased; (2) apparent PHT elimination half‐life increased; (3) apparent mean PHT serum concentration per unit dose increased; (4) apparent rate of excretion of p‐hydroxyphenyl‐phenylhydantoin (p‐HPPH) decreased; (5) apparent rate of excretion of PHT dihydrodiol increased; and (6) apparent PHT total clearance and elimination half‐life and apparent p‐HPPH rate of excretion were dose dependent. Phenytoin apparent pharmacokinetic and biotransformation values undergo a typical series of changes after beginning monotherapy at typical dosing rates, because PHT's dose‐dependent pharmacokinetics result in differing apparent vaiues as the serum concentration rises to steady state. Stable iostope methods are particularly suitable for investigating

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02799.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Six healthy adults receiving no other medications were given tracer doses of 90 mg of stable isotope‐labeled phenobarbital (PB) intravenously before, and four weeks after, and 12 weeks after beginning therapy. Serum samples were collected for 96 hours after each injection, and the concentration of stable isotope‐labeled PB in each sample was determined by gas chromatographic mass spectrometry. The volume of distribution, elimination half‐life, and total clearance of PB did not differ significantly on any of the three occasions measured. Phenobarbital clearance did not correlate significantly with total PB serum concentration. Clearances determined from single‐dose studies before beginning PB therapy accurately predicted steady‐state PB serum concentrations. Therefore, it is not necessary to adjust PB dosage for time‐dependent or dose‐dependent changes in clearance during monotherapy. In addition, clearance or serum concentration determined at one dosing rate directly predicts serum concentration at anothe

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02800.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Stable isotope labeled tracer doses of phenytoin (PHT) and phenobarbital (PB) were given intravenously before and four and 12 weeks after beginning monotherapy in two groups of six patients. Phenytoin demonstrated nonlinear pharmacokinetics, while PB demonstrated linear pharmacokinetics. Each of the 36 sets of tracer dose serum concentration versus time data points appeared linear during the elimination phase on semilog plots, and each demonstrated a high degree of linearity using semilog regression analysis(r2=.977‐.999, P<.001, for PHT;r2=.791‐.996, P<.005, for PB). We conclude tracer doses administered at steady‐state serum concentration will exhibit linear serum concentration versus time relationships on semilog plots regardless of whether the steady‐state serum concentration is in the linear or the nonlinear portion of a drug's dose versus steady‐state serum concentration relationship. The mechanism and implications of this conclusion are

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02801.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1985.tb02803.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY