Indomethacin- and desamino-8-D-arginine vasopressin-induced lithium reabsorption is not amiloride sensitive in humans.
This study was undertaken to analyze whether the mechanism of decreased fractional lithium excretion (FELi) induced in humans by the prostaglandin synthesis inhibitor indomethacin and the vasopressin analog desamino-8-D-arginine vasopressin (d-DAVP) is amiloride inhibitable. Eight sodium-restricted (10 mmol/day) healthy volunteers underwent clearance studies to evaluate the effects of indomethacin (50 mg tid for 6 days), amiloride (10 mg twice before the clearance study) and d-DAVP (4 micrograms, i.v.), and combinations of these drugs. Despite the sodium restriction, amiloride had no effect on FELi, although the dosage was sufficient to cause a 6-fold increase in sodium excretion, and potassium retention. Compared to a base-line value of 27.9 +/- 2.1%, FELi fell to 20.7 +/- 2.1% after indomethacin (P < .01) and to 22.4 +/- 1.5% after d-DAVP (P < .01). When d-DAVP was administered during indomethacin, the FELi fell to 18.0 +/- 1.4%. Compared to indomethacin alone, this represented no significant further change. Amiloride did not prevent the fall in FELi caused by indomethacin or d-DAVP or both. These data indicate that in humans, 1) sodium restriction does not cause amiloride-sensitive lithium reabsorption, and 2) the lithium reabsorption caused by d-DAVP and indomethacin is not amiloride sensitive.
Bijlsma
J A
JA
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Koomans
H A
HA
Boer
W H
WH
Dorhout Mees
E J
EJ
van Rijn
H J
HJ
D000042:Absorption; D000328:Adult; D000584:Amiloride / Q000494:pharmacology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008094:Lithium / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D012016:Reference Values; D012964:Sodium / Q000652:urine
D000584:Amiloride; D008094:Lithium; D012964:Sodium; D003894:Deamino Arginine Vasopressin; D007213:Indomethacin