NAPROXEN FREE PLASMA-CONCENTRATIONS AND UNBOUND FRACTIONS IN PATIENTS WITH OSTEOARTHRITIS - RELATION TO AGE, SEX, EFFICACY, AND ADVERSE EVENTS

被引:12
作者
HUNDAL, O
RUGSTAD, HE
HUSBY, G
机构
[1] UNIV TROMSO HOSP,DEPT RHEUMATOL,N-9012 TROMSO,NORWAY
[2] NATL HOSP NORWAY,DEPT CLIN PHARMACOL,OSLO 1,NORWAY
[3] UNIV OSLO,DEPT PHARM,PHARMACEUT CHEM SECT,OSLO 3,NORWAY
关键词
NAPROXEN; OSTEOARTHRITIS; FREE CONCENTRATION; UNBOUND FRACTION; EFFICACY; ADVERSE EVENTS;
D O I
10.1097/00007691-199111000-00002
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Plasma samples from 237 patients with osteoarthritis treated with 750 mg naproxen daily were obtained after four weeks of active therapy. The samples were subjected to equilibrium dialysis, analyzed by high-performance liquid chromatography, and free concentrations and unbound fractions were determined. Within the free plasma concentration range in this large patient group, we could detect no association between free naproxen concentration and efficacy score or between free concentrations and adverse events. Free concentrations were 0.295 +/- 0.260-mu-g/ml (mean +/- SD) and unbound fractions were 0.33 +/- 0.24%. Females had 65% higher free concentration compared to males (p < 0.001). For females, but not for males, there was a statistically significant correlation (p < 0.005) between age and free concentration. The free concentration was estimated to be 88% higher in an 80-year-old female compared to a 50-year-old. Females had a 41% higher unbound fraction than males (p < 0.005). For females, but not for males, a statistically significant relationship between age and unbound fraction was found. The unbound fraction was estimated to be 62% higher in an 80-year-old female than in a 50-year-old.
引用
收藏
页码:478 / 484
页数:7
相关论文
共 44 条
[1]   PLASMA AND SYNOVIAL-FLUID KINETICS OF FLURBIPROFEN IN RHEUMATOID-ARTHRITIS [J].
AARONS, L ;
SALISBURY, R ;
ALAMSIDDIQI, M ;
TAYLOR, L ;
GRENNAN, DM .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1986, 21 (02) :155-163
[2]   EFFECT OF PROTEIN-CONCENTRATION ON THE BINDING OF DRUGS TO HUMAN-SERUM ALBUMIN .1. SULFADIAZINE, SALICYLATE AND PHENYLBUTAZONE [J].
BOOBIS, SW ;
CHIGNELL, CF .
BIOCHEMICAL PHARMACOLOGY, 1979, 28 (06) :751-756
[3]   DETERMINATION OF CREATININE BY MEANS OF AUTOMATIC CHEMICAL ANALYSIS [J].
CHASSON, AL ;
STANLEY, MA ;
GRADY, HJ .
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 1961, 35 (01) :83-&
[4]   AGE CHANGES IN GLOMERULAR FILTRATION RATE, EFFECTIVE RENAL PLASMA FLOW, AND TUBULAR EXCRETORY CAPACITY IN ADULT MALES [J].
DAVIES, DF ;
SHOCK, NW .
JOURNAL OF CLINICAL INVESTIGATION, 1950, 29 (05) :496-507
[5]   RELATIONSHIP OF SERUM NAPROXEN CONCENTRATION TO EFFICACY IN RHEUMATOID-ARTHRITIS [J].
DAY, RO ;
FURST, DE ;
DROMGOOLE, SH ;
KAMM, B ;
ROE, R ;
PAULUS, HE .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1982, 31 (06) :733-740
[6]   PENETRATION OF NAPROXEN AND SALICYLATE INTO INFLAMMATORY EXUDATES IN RAT [J].
DOHERTY, NS ;
ANTTILA, M ;
DEAN, PB .
ANNALS OF THE RHEUMATIC DISEASES, 1977, 36 (03) :244-248
[7]   ALBUMIN STANDARDS AND MEASUREMENT OF SERUM ALBUMIN WITH BROMCRESOL GREEN [J].
DOUMAS, BT ;
WATSON, WA ;
BIGGS, HG .
CLINICA CHIMICA ACTA, 1971, 31 (01) :87-&
[8]  
FURST DE, 1985, NONSTEROIDAL ANTIINF, P141
[9]   MECHANISM OF ACTION OF NONSTEROIDAL ANTI-INFLAMMATORY AGENTS [J].
GOODWIN, JS .
AMERICAN JOURNAL OF MEDICINE, 1984, 77 (1A) :57-64
[10]  
GORNALL AG, 1949, J BIOL CHEM, V177, P751