Acute haemodynamic and renal effects of cyclosporin and indomethacin in man.
A single oral dose of cyclosporin (12 mg/kg) was given to healthy volunteers (n = 9) on day 2 with or without indomethacin pretreatment (100 mg day 1 + 100 mg day 2). All parameters reported were analysed after a water-loading protocol on day 2. As a peak drug effect within 4 h of drug ingestion on day 2 cyclosporin on its own increased mean arterial pressure by 13% (P < 0.05) without causing any sodium retention or renal vasoconstriction. Indomethacin pretreatment did not accentuate this hypertensive effect of cyclosporin. The earliest renal effect observed with cyclosporin on day 2 was on water handling with a marked antidiuretic effect. Free-water clearance decreased by a maximum of 48% (P < 0.05) following cyclosporin. Indomethacin pretreatment induced a similar antidiuresis on day 2 but cyclosporin did not augment this antidiuresis any further. This suggests that inhibition of vasodilator prostaglandins within the kidneys may mediate the antidiuretic effect of cyclosporin such that in the presence of indomethacin, cyclosporin had no additional effect. The inhibition of intrarenal prostaglandins by a single dose of indomethacin did not, however, produce any acute cyclosporin-induced change in glomerular filtration rate or renal blood flow.
Sturrock
N D
ND
Department of Pharmacology and Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee UK.
Lang
C C
CC
Clark
G
G
Struthers
A D
AD
D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000502:physiology; D004231:Diuresis / Q000187:drug effects; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects
D016572:Cyclosporine; D015232:Dinoprostone; D007213:Indomethacin