ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01909.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01910.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01911.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Moricizine, a unique Class I antiarrhythmic agent, was orally administered with and without a meal to 24 healthy male subjects to determine the effect of food on moricizine absorption and bioavailability. Relative to the fasting state, a standardized breakfast delayed the time to peak plasma moricizine concentration (1.2 vs. 0.9 hr; P<.03) and lowered peak plasma moricizine concentration by 24% (0.55 vs. 0.72 μg/mL; P<.03). Bioavailability, as measured by area under the plasma moricizine concentration versus time curve, was not significantly altered by the meal

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01912.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Fasting lipid profiles were measured in 20 selected patients the day of and after cardiac catheterization in EDTA tubes. Samples were randomly labelled A or B, centrifuged, and stored at 3° Centigrade. Lipid profiles were analyzed by a laboratory, which was participating in the Center for Disease Control Lipid Standardization Program, by using standard methods. The coefficients of variation for repeated measurements were: cholesterol = 1.9%, triglycerides = 3.6%, HDL cholesterol = 4.3%, and VLDL and LDL cholesterol = 2.6%. Data were evaluated by a two‐tailed pairedt‐test and correlation coefficient. The total cholesterol was significantly lower (P<.001) the day after cardiac catheterization as was the LDL cholesterol (P<.002). Both VLDL and HDL cholesterol and triglycerides were lower, but these were not statistically significant. The mean dose of heparin was 3500 ± 1469 units, and the mean dose of contrast was 181 ± 30 cc. The total dose of heparin or contrast did not correlate with any change in lipid profiles. These results have implications on the number and timing of venous blood sampling for lipid measurements in regard to diagnosis and treatment of hyperlipidemia. Lipid proxies should not be drawn after cardiac catheterization but rather before and/or in the free‐livi

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01913.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01914.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Paracetamol is an analgetic drug with additive effect if combined with indomethacin. In rat experiments, paracetamol has been shown to be gastro‐protective, and in animal experiments, indomethacin blood levels decreased during combined treatment with paracetamol. The kinetic effect of paracetamol on indomethacin has been investigated in ten healthy volunteers. The mean area under the indomethacin plasma concentration curve AUC 0‐α was 10.4 ± 4.21 ug/mL × hr and did not change during combined paracetamol treatment (11.0 ± 3.24 ug/mL × hrns). Paracetamol levels were unchanged. In this study, no evidence was found that paracetamol can alter the pharmacokinetics of indomethacin i

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01915.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

This study compared the pharmacokinetics of flurbiprofen (F) and three major metabolites in patients with end‐stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD) with the pharmacokinetics of F in normal subjects. A single 100‐mg dose of F was administered to each of nine normal subjects and eight ESRD subjects. Blood and urine samples were collected in both groups; serial and end of dwell dialysate samples were obtained from the ESRD subjects. Plasma was analyzed for both the R and S optical isomers of F and its major metabolite, 4′‐hydroxy‐flurbiprofen (HF). Urine and dialysate were analyzed for F and three known metabolites. Plasma concentrations of F in the ESRD subjects were approximately 50% of the values obtained from the normal subjects(P<.05). Flurbiprofen half‐life and Tmax were not different. Elimination of HF was reduced in ESRD subjects. Urinary data suggest that HF was the major metabolite excreted (36% of the dose) in normal subjects whereas 3′, 4′ ‐dihydroxy‐flurbiprofen was the major metabolite (9% of the dose) excreted in the ESRD group. Mean urinary recovery of the dose was 73% in the normal subjects, but only 16% in ESRD subjects. Neither F nor its metabolites were detected in dialysate. Small enantiomer differences were seen. This study suggests that ESRD subjects have lower plasma levels of F than normal subjects when administered equal size doses. Accumulation of metabolites may occur in ESRD subjects upon multiple dosing. Enantiomer differences are not cli

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01916.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

A selective thromboxane A2(TXA2) receptor blocking agent, vapiprost, was orally administered to healthy male Japanese volunteers to investigate the pharmacokinetic and pharmacodynamic properties. The time‐profile of vapiprost concentration in plasma was determined and the effects of the drug on platelet aggregation in platelet‐rich plasma (PRP) induced by a stable TXA2receptor agonist U‐46619, adenosine diphosphate (ADP) and collagen, and platelet aggregation in whole blood induced by U‐46619 ex vivo were simultaneously examined and compared. In the single‐dose study (5, 10, and 20 mg/man) the plasma concentrations of the drug were fitted well to a one‐compartment open model with a first‐order absorption. The area under plasma concentration‐time curve (AUC) and maximum plasma concentration (Cmax) showed dose‐related increases, whereas the mean elimination half‐lives (t1/2) remained approximately constant within the range of 0.99–1.1 hour. The drug was hardly recovered unchanged in urine. The platelet aggregation in PRP induced by collagen or U‐46619 and the secondary aggregation by ADP were inhibited; that induced by U‐46619 was the most specifically and completely inhibited at 2 hours after administration of any dose. The duration for maintaining the significant inhibition tended to depend on the dose and ranged from 24 to 36 hours after administration, which was much longer than expected from the plasma concentration of drug. The time‐profile of inhibiting whole blood platelet aggregation that was induced by U‐46619 was almost parallel to that of platelet aggregation in PRP by the same aggregant. The bleeding time was slightly prolonged 2 and 8 hours after administrations of 10 and 20 mg, respectively. In the multiple‐dose study (20 mg/man twice daily for 5 days; 9 doses in total) plasma concentration of the drug after each administration showed a good conformity with the simulation curve worked out using the pharmacokinetic parameters that were obtained at the time of the initial dose. This indicated that repeated administrations did not result in accumulation. Throughout the administration period, almost the same extent of inhibiting platelet aggregation by each aggregant was maintained. After the final administration almost complete inhibition of platelet aggregations both in PRP and whole blood by U‐46619 was maintained till 48 hours and a significant inhibition lasted over 72 hours, which also surpassed the duration of maintaining plasma concentration. The bleeding time showed no significant prolongation. No abnormality attributable to the test drug was found in the routine laboratory tests, subjective and objective findings, vital signs including blood pressure, pulse rate, and body temperature, and ECG except that one of six subjects in the multiple‐dose study showed a slight elevation of liver function test parameters. Drug administration was discontinued in this subject after the eighth dose. These parameters returned to the normal values within 1 week after the discontinuation. In conclusion, oral administration of vapiprost was well‐tolerated with long‐lasting inhibition of platelet

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01917.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01918.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY