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Titolo:
L-ARGININE-INDUCED VASODILATION IN HEALTHY HUMANS - PHARMACOKINETIC-PHARMACODYNAMIC RELATIONSHIP
Autore:
BODEBOGER SM; BOGER RH; GALLAND A; TSIKAS D; FROLICH JC;
Indirizzi:
HANNOVER MED SCH,INST CLIN PHARMACOL D-30623 HANNOVER GERMANY
Titolo Testata:
British journal of clinical pharmacology
fascicolo: 5, volume: 46, anno: 1998,
pagine: 489 - 497
SICI:
0306-5251(1998)46:5<489:LVIHH->2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHESIS; ORAL L-ARGININE; CHROMATOGRAPHY-MASS-SPECTROMETRY; ENDOTHELIUM-DEPENDENT DILATION; INHIBITS PLATELET-AGGREGATION; IMPEDANCE CARDIOGRAPHY; DIETARY ARGININE; GROWTH-HORMONE; STROKE VOLUME; DOUBLE-BLIND;
Keywords:
NITRIC OXIDE; ENDOTHELIUM; PERIPHERAL RESISTANCE; IMPEDANCE CARDIOGRAPHY; NON-COMPARTMENTAL ANALYSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
S.M. Bodeboger et al., "L-ARGININE-INDUCED VASODILATION IN HEALTHY HUMANS - PHARMACOKINETIC-PHARMACODYNAMIC RELATIONSHIP", British journal of clinical pharmacology, 46(5), 1998, pp. 489-497

Abstract

Aims Administration of L-arginine by intravenous infusion or via oralabsorption has been shown to induce peripheral vasodilation in humans, and to improve endothelium-dependent vasodilation. We investigated the pharmacokinetics and pharmacokinetic-pharmacodynamic relationship of L-arginine after a single intravenous infusion of 30 g or 6 g, or after a single oral application of 6 g, as compared with the respective placebo, in eight healthy male human subjects. Methods L-arginine levels were determined by h.p.l.c. The vasodilator effects of L-arginine were assessed non-invasively by blood pressure monitoring and impedancecardiography. Urinary nitrate and cyclic GMP excretion rates were measured as non-invasive indicators of endogenous NO production. Results Plasma L-arginine levels increased to (mean+/-s.e.mean) 6223+/-407 (range, 5100-7680) and 822+/-59 (527-955) mu mol l(-1) after intravenous infusion of 30 g and 6 g L-arginine, respectively, and to 310+/-152 (118-1219) mu mol l(-1) after oral ingestion of 6 g L-arginine. Oral bioavailability of L-arginine was 68+/-9 (51-87)%. Clearance was 544+/-24(440-620), 894+/-164 (470-1190), and 1018+/-230 (710-2130) ml min(-1), and elimination half-life was calculated as 41.6+/-2.3 (34-55), 59.6/-9.1 (24-98), and 79.5+/-9.3 (50-121) min, respectively, for 30 g i.v., 6 g i.v., and 6 g p.o. of L-arginine. Blood pressure and total peripheral resistance were significantly decreased after intravenous infusion of 30 g L-arginine by 4.4+/-1.4% and 10.4+/-3.6%, respectively, but were not significantly changed after oral or intravenous administration of 6 g L-arginine. L-arginine (30 g) also significantly increasedurinary nitrate and cyclic GMP excretion rates by 97+/-28 and 66+/-20%, respectively. After infusion of 6 g L-arginine, urinary nitrate excretion also significantly increased, (nitrate by 47+/-12% [P<0.05], cyclic GMP by 67+/-47% [P=ns]), although to a lesser and more variable extent than after 30 g of L-arginine. The onset and the duration of thevasodilator effect of L-arginine and its effects on endogenous NO production closely corresponded to the plasma concentration half-life of L-arginine, as indicated by ai; equilibration half-life of 6+/-2 (3.7-8.4) min between plasma concentration and effect in pharmacokinetic-pharmacodynamic analysis, and the lack of hysteresis in the plasma concentration-versus-effect plot. Conclusions The vascular effects of L-arginine are closely correlated with its plasma concentrations. These data may provide a basis for the utilization of L-arginine in cardiovascular diseases.

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Documento generato il 07/04/20 alle ore 22:39:48