Indomethacin increases renal lithium reabsorption in man.
We examined the effect of semi-acute indomethacin (4 x 50 mg orally during the preceding 27 h) on renal function parameters, including fractional lithium reabsorption (FRLi) in seven healthy subjects during a 200 mmol and a 40 mmol sodium diet. Studies were carried out during maximal water diuresis. During the sodium-rich diet, indomethacin raised minimal urine osmolality from 61 +/- 1 to 72 +/- 2 mosm/kg (P less than 0.05), and during the sodium-restricted diet from 55 +/- 3 to 93 +/- 6 mosm/kg (P less than 0.01). Indomethacin reduced maximal free water clearance only during the low-sodium diet, and had no consistent effect on inulin clearance and the fractional excretions of sodium, phosphate and uric acid. Nevertheless, FRLi rose substantially, from 71 +/- 2% to 75 +/- 2% (P less than 0.01) and from 75 +/- 2% to 81 +/- 2% (P less than 0.01) during high- and low-sodium diets respectively. During either diet, indomethacin caused a significant reduction of 24-h urine PGE2 excretion. Since indomethacin is not supposed to influence proximal tubular sodium reabsorption, the rise in lithium reabsorption occurred beyond this nephron level, presumably in the loop of Henle. Clearly, the FRLi cannot be used as a quantitative marker of proximal tubular sodium reabsorption in humans in all conditions.
Rabelink
A J
AJ
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; D015232:Dinoprostone / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects*; D007686:Kidney Tubules, Distal / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000493:pharmacokinetics*; D016651:Lithium Carbonate; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D012982:Sodium, Dietary / Q000008:administration & dosage
D012982:Sodium, Dietary; D016651:Lithium Carbonate; D008094:Lithium; D015232:Dinoprostone; D007213:Indomethacin