ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03329.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03330.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The purposes of this investigation were to demonstrate how computer simulations may be employed to extrapolate data obtained from a single intravenous digoxin dose to multiple oral dosing patterns and how these simulations may apply to clinical situations. The intravenous data were obtained from a previous study of the pharmacokinetics of serum digoxin and its inotropic response (derived from systolic intervals) in 12 normal male volunteers. The simulations were applied to various clinical situations including variations in oral dosing, alternate loading doses, no loading versus loading dose, and intravenous versus oral dosing. A nonlinear relationship was found between response and the post‐distribution serum digoxin concentration in the therapeutic range. Thus, the increase in inotropic response is less than proportional to the increase in digoxin concentration in serum. This nonlinear relationship has several important clinical implications for loading and maintenance dosing protocols. Such concepts may be important relative to more rational clinical use of digoxin and to decreasing digoxin toxicit

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03331.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The influence of indomethacin on a reduction in forearm blood flow (FBF) induced by propranolol was investigated in eight healthy subjects. Indomethacin was orally administered (75 mg daily for 3 days) in a randomized cross‐over design. Blood pressure (BP) was slightly decreased after a single oral administration of propranolol (40 mg) alone. However BP was slightly increased after the drug with indomethacin pretreatment. FBF was significantly decreased after propranolol with or without indomethacin. No significant difference was observed in FBF before or after propranolol between both groups. Plasma renin activity (PRA) was reduced by indomethacin pretreatment. These results suggest that the reduction in FBF induced by propranolol is not augmented with indomethaci

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03332.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The effect of advancing age on the kinetics of the antiarrhythmic agent mexiletine was studied by comparing various kinetic parameters calculated after administration of a single oral dose of mexiletine hydrochloride to seven elderly and eight young healthy volunteers. The rate of absorption of the drug from the gastrointestinal tract was significantly slower in the elderly (1.37 ± 0.51 hr−1) than in the young group (2.25 ± 0.79 hr−1). The mean values for elimination half‐life and oral clearance were 12.3 ± 3.7 hr and 10.3 ± 5.4 mL/min/kg respectively in the young group and 14.4 ± 4.5 hr and 8.5 ± 2.9 mL/min/kg respectively in the elderly group. Neither of these parameters was significantly different between the two groups. The amount of mexiletine eliminated in urine up to 48 hours postdose was identical in both groups and represented less than 5% of the administered dose. It is concluded that the age‐related modifications in the kinetics of mexiletine are not clinically important during chronic administratio

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03333.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

In a double‐blind, randomized, cross‐over study in 23 diabetic patients, insulin treated (N = 11) or noninsulin treated (N = 12), with mild to moderate hypertension, the hypotensive effects of captopril and atenolol were compared. Five patients had overt diabetic nephropathy. All patients received 50 mg twice daily of either drug. Treatment periods lasted 6 weeks and were preceded and separated by a placebo period. Two patients dropped out, one because of intermittent claudication during atenolol, one with cardiac arrhythmia during placebo. Blood pressure was reduced from 165 ± 5/96 ± 1 to 154 ± 5/89 ± 2 mmHg (mean ± SEM: P<0.01) during captopril and from 171 ± 5/98 ± 1 to 159 ± 6/89 ± 2 mmHg (P<0.01) during atenolol. These antihypertensive effects are not significantly different. There was a wide inter‐ and intraindividual variation in hypotensive response to both drugs, which may have important consequences for treatment strategies. No consistent differences between insulin and noninsulin treated patients were seen. Parameters of glycemic control did not change during any therapy, neither in insulin treated nor in non‐insulin treated patients. Albuminuria and renal function did not change. During captopril treatment one patient complained of a non‐productive cough. Two patients experienced a severe hypoglycemic reaction during atenolol. No other major side‐effects were seen. In conclusion, this study showed equal hypotensive effectivity of 100 mg captopril and 100 mg atenolol daily in hypertensive diabetics, without evident effect

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03334.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Using a sensitive and specific radioimmunoassay the pharmacokinetic disposition of clonidine was determined in hypertensive patients after a single dose and then after 5, 28 and 56 days of chronic dosing with 75 μg bd. Following a single dose of clonidine maximal plasma concentrations of 0.34 ± 0.06 ng/ml were achieved after 3.6 ± 1.2 hours. After 5 days of repetitive dosing the maximal concentration was significantly higher, 0.66 ± 0.06 ng/ml and remained so throughout chronic therapy (P= 0.018). The AUC, Tmaxand T1/2did not differ significantly between the acute dose and the chronic dosing pharmacokinetic studies. Clonidine also produced a significant fall in blood pressure. Supine diastolic blood pressure fell from 106 ± 5 mmHg predose to 99 ± 6 mmHg 2 hours after the first dose (P<0.05). The corresponding values after cyclopenthiazide alone were 108 ± 8 and 105 ± 8 mmHg (P= 0.13). Similar falls in blood pressure were produced during chronic

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03335.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The effects of chronic administration of traxanox sodium (traxanox) on blood pressure and serum uric acid level were investigated in 15 patients who had mild to moderate hypertension. Traxanox or its placebo was orally administered in a single‐blind protocol. Blood pressure was significantly reduced from baseline after treatment with traxanox. The serum uric acid level after drug administration was significantly lower than with placebo whereas urinary uric acid excretion was significantly greater and uric acid clearance tended to be greater. These results indicate that chronic administration of traxanox reduces serum uric acid level as well as blood pressure in patients with mild to moderate hypertension. This reduction in serum uric acid is due in part to a traxanox‐induced elevation of urinary uric acid excret

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03336.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

To determine the single‐ and multiple‐dose ceftazidime kinetics, we administered ceftazidime, 2 gm intravenous bolus every 12 hours, to 14 infected Chinese patients with various degrees of renal function. Blood samples were drawn in serial after the first and 7th dose and serum ceftazidime concentrations were measured by high pressure liquid chromatography. Ceftazidime concentration‐time data were fitted to a two‐compartment model with a nonlinear regression program. Ceftazidime kinetics was unaltered by repeated dosing. Both total body clearance and elimination rate constant of ceftazidime decrease significantly in proportion to the creatinine clearance estimated by Bjornsson's method. Renal insufficiency did not modify the steady‐state volume of distribution (Vdss) of ceftazidime which, however, appeared to be larger than those reported previously. This larger Vdss may be explained by acute infection process, confinement to bed, and increased extracellular fluid volume as a result of hypoalbuminemia. Our study indicates the estimated creatinine clearance as a useful guide to ceftazidime dosage adjustment and also emphasizes the clinical relevance of conducting kinetic studies of antibiotics in infected

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03337.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The bioavailability of citrate from two different preparations of potassium citrate was examined in eighteen normal volunteers during three phases of study. After stabilization on a constant metabolic diet, subjects took a single dose of placebo, “slow‐release” potassium citrate tablets (60 meq) or rapid‐release liquid potassium citrate preparation (60 meq). Timed urine specimens were collected for 24 hours and analyzed for citrate, potassium, and pH. Similar biochemical findings were observed following administration of the two different preparations with the onset and decline of changes being slightly more rapid for the liquid potassium citrate than the tablet preparation. These equivalent bioavailability data indicate that the liquid preparation is a comparable therapeutic alternative to the tabl

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03338.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY