KINETIC-DYNAMIC RELATIONS AND INDIVIDUAL-RESPONSES TO ENALAPRIL

被引:63
作者
DONNELLY, R [1 ]
MEREDITH, PA [1 ]
ELLIOTT, HL [1 ]
REID, JL [1 ]
机构
[1] STOBHILL GEN HOSP,DEPT MED & THERAPEUT,GLASGOW G21 3UW,SCOTLAND
关键词
Antihypertensive agents; Enalapril; Essential hypertension; Pharmacokinetics;
D O I
10.1161/01.HYP.15.3.301
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Pharmacokinetic and pharmacodynamic variability largely account for interindividual differences in the response to antihypertensive drugs including angiotensin converting enzyme inhibitors. The factors determining the response to enalapril have been investigated in a placebo-controlled study in essential hypertension. The effects of placebo, the initial dose of enalapril, and long-term (1 and 6 weeks) treatment with enalapril were studied in 13 subjects. By using an integrated kinetic-dynamic model that incorporates a parameter for saturable protein binding, individual responses for blood pressure reduction and angiotensin converting enzyme inhibition were characterized in terms of the maximum effect (Emax) and the drug concentration required to produce 50% of Emax (Ce50). In individual subjects, plasma enalaprilat concentrations could be correlated with falls in blood pressure and changes in plasma angiotensin converting enzyme activity. For the group, Emax was -46.1±16.5 and -19.7±3.8 mm Hg for systolic and diastolic blood pressure, respectively, and the corresponding Ce50 values were 66.1±20.2 and 61.6±22.5 ng/ml. For angiotensin converting enzyme inhibition, Emax (%) and Ce50 (ng/ml) were, respectively, 102.4±5 and 19.8±13 after the first dose, 103±5 and 33.4±20.3 after 1 week, and 101.3±2.2 and 31.3±18.9 after 6 weeks. There was no relation between the responsiveness to enalapril (Emax or Ce50) and patient age or plasma renin activity, but there was a significant positive correlation between Emax and the pretreatment blood pressure. In individual subjects, Emax (first dose) was directly correlated with Emax after 1 and 6 weeks. This study, which incorporated kinetic as well as dynamic information to characterize the antihypertensive response to enalapril, has identified enalaprilat concentration-effect relations in individual hypertensive subjects.
引用
收藏
页码:301 / 309
页数:9
相关论文
共 29 条
[1]   INDIVIDUAL-RESPONSES TO CONVERTING ENZYME-INHIBITORS AND CALCIUM-ANTAGONISTS [J].
BIDIVILLE, J ;
NUSSBERGER, J ;
WAEBER, G ;
PORCHET, M ;
WAEBER, B ;
BRUNNER, HR .
HYPERTENSION, 1988, 11 (02) :166-173
[2]   ENALAPRIL MALEATE AND A LYSINE ANALOG (MK-521) IN NORMAL VOLUNTEERS - RELATIONSHIP BETWEEN PLASMA DRUG LEVELS AND THE RENIN-ANGIOTENSIN SYSTEM [J].
BIOLLAZ, J ;
SCHELLING, JL ;
COMBES, BJD ;
BRUNNER, DB ;
DESPONDS, G ;
BRUNNER, HR ;
ULM, EH ;
HICHENS, M ;
GOMEZ, HJ .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1982, 14 (03) :363-368
[3]  
Brunner H R, 1983, J Hypertens Suppl, V1, P103
[4]   CLINICAL USE OF AN ORALLY ACTING CONVERTING ENZYME-INHIBITOR - CAPTOPRIL [J].
BRUNNER, HR ;
GAVRAS, H ;
WAEBER, B ;
TEXTOR, SC ;
TURINI, GA ;
WAUTERS, JP .
HYPERTENSION, 1980, 2 (04) :558-566
[5]  
CHIKNAS SG, 1979, CLIN CHEM, V25, P1259
[6]   SIMULTANEOUS RADIOENZYMATIC DETERMINATION OF PLASMA AND TISSUE ADRENALINE, NORADRENALINE AND DOPAMINE WITHIN FEMTOMOLE RANGE [J].
DAPRADA, M ;
ZURCHER, G .
LIFE SCIENCES, 1976, 19 (08) :1161-1174
[7]   AN OVERVIEW OF THE CLINICAL-PHARMACOLOGY OF ENALAPRIL [J].
DAVIES, RO ;
GOMEZ, HJ ;
IRVIN, JD ;
WALKER, JF .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1984, 18 :S215-S229
[8]   HUMORAL AND RENAL EFFECTS OF MK-421 (ENALAPRIL) IN HYPERTENSIVE SUBJECTS [J].
DELEEUW, PW ;
HOOGMA, RPLM ;
VANSOEST, GAW ;
TCHANG, PT ;
BIRKENHAGER, WH .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1983, 5 (05) :731-736
[9]  
DERKX FHM, 1972, CLIN EXP HYPERTENS, V2, P575
[10]   PHARMACOKINETICS OF THE CONVERTING-ENZYME-INHIBITOR CILAZAPRIL IN NORMAL VOLUNTEERS AND THE RELATIONSHIP TO ENZYME-INHIBITION - DEVELOPMENT OF A MATHEMATICAL-MODEL [J].
FRANCIS, RJ ;
BROWN, AN ;
KLER, L ;
DAMORE, TF ;
NUSSBERGER, J ;
WAEBER, B ;
BRUNNER, HR .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1987, 9 (01) :32-38